| 1. |
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| 2. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 3. |
- Kristan, Matej, et al.
(författare)
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The first visual object tracking segmentation VOTS2023 challenge results
- 2023
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Ingår i: 2023 IEEE/CVF International conference on computer vision workshops (ICCVW). - : Institute of Electrical and Electronics Engineers Inc.. - 9798350307443 - 9798350307450 ; , s. 1788-1810
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking Segmentation VOTS2023 challenge is the eleventh annual tracker benchmarking activity of the VOT initiative. This challenge is the first to merge short-term and long-term as well as single-target and multiple-target tracking with segmentation masks as the only target location specification. A new dataset was created; the ground truth has been withheld to prevent overfitting. New performance measures and evaluation protocols have been created along with a new toolkit and an evaluation server. Results of the presented 47 trackers indicate that modern tracking frameworks are well-suited to deal with convergence of short-term and long-term tracking and that multiple and single target tracking can be considered a single problem. A leaderboard, with participating trackers details, the source code, the datasets, and the evaluation kit are publicly available at the challenge website1
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| 4. |
- Li, Duan, et al.
(författare)
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Dense and strong ZrO2 ceramics fully densified in <15 min
- 2019
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Ingår i: Advances in Applied Ceramics. - : Informa UK Limited. - 1743-6753 .- 1743-6761. ; 118:1-2, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- Crack-free zirconia ceramics were consolidated via sintering by intense thermal radiation (SITR) approach at 1600–1700°C for 3–5 min. The resulted ceramic bulks can achieve a relative density up to 99.6% with a grain size of 300–1200 nm. Their bending strength, Vickers hardness and indentation toughness values are up to 1244 ± 139 MPa, 13.3 ± 0.3 GPa and 5.5 ± 0.1 MPa m1/2, respectively. Quantitative Raman and XRD analysis show the presence of minor m phase on the natural surface (<7%), fracture surface (<10%) and indentation areas (<15%). It reveals that the SITR method is efficient for rapidly manufacturing zirconia ceramics with desired density, fine grained microstructure and good mechanical properties that are strongly demanded in dental applications.
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| 5. |
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| 6. |
- Liu, Junwei, et al.
(författare)
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Polymer synergy for efficient hole transport in solar cells and photodetectors
- 2023
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Ingår i: Energy & Environmental Science. - : ROYAL SOC CHEMISTRY. - 1754-5692 .- 1754-5706.
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Tidskriftsartikel (refereegranskat)abstract
- Hole transport materials (HTMs) have greatly advanced the progress of solution-based electronic devices in the past few years. Nevertheless, most devices employing dopant-free organic HTMs can only deliver inferior performance. In this work, we introduced a novel "polymer synergy" strategy to develop versatile dopant-free polymer HTMs for quantum dot/perovskite solar cells and photodetectors. With this synergy strategy, the optical, electrical and aggregation properties of polymer HTMs can be modulated, resulting in complementary absorption, high hole mobility, favorable energy landscape and moderate aggregation. Moreover, a clear orientational transition was observed for the developed HTMs with a 9-fold increase in the face-on/edge-on ratio, providing a highway-like carrier transport for electronic devices, as revealed by in situ characterization and ultrafast transient absorption. With these benefits, the photovoltaic and photodetection performance of quantum dot devices were boosted from 11.8% to 13.5% and from 2.95 x 10(12) to 3.41 x 10(13) Jones (over a 10-fold increase), respectively. Furthermore, the developed polymer HTMs can also significantly enhance the photovoltaic and photodetection performance of perovskite devices from 15.1% to 22.7% and from 2.7 x 10(12) to 2.17 x 10(13)Jones with the same device structure, indicating their great application potential in the emerging optoelectronics.
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| 7. |
- Wang, Jintian, et al.
(författare)
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An experimental study on abnormal vibration of metro trains caused by out-of-round wheels
- 2023
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Ingår i: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 237:2, s. 224-231
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Tidskriftsartikel (refereegranskat)abstract
- Out-of-round (OOR) wheel often happens to trains, which can cause abnormal vibration. To develop effective countermeasures to minimize the abnormal vibration, it is necessary to study how the wheel OOR wear affects the vehicle vibration. This paper performs an experimental study on the abnormal vibration characteristics of metro trains with out-of-round wheels. The vibration characteristics is identified by the general survey of wheel roughness from special tests. The statistic wheel wear values of all the vehicles in an operating metro lines are studied to investigate the relationship between the wheel wear and the operating mileage. Several re-profiling strategies are implemented to eliminate the abnormal vibration caused by wheel OOR. The results show that the root cause of the abnormal vibration and deterioration of ride comfort is the car-body flexible resonance excited by the wheel OOR wear. Wheel re-profiling is the most effective measure for reducing the vehicle abnormal vibration. By re-profiling all the wheels of a tested metro vehicle, the ride comfort can be improved by 35% ∼ 40% and the axle-box acceleration can be reduced by 40%.
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| 8. |
- Yin, Bin, et al.
(författare)
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Solution-processed bulk heterojunction organic solar cells based on an oligothiophene derivative
- 2010
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Ingår i: Applied Physics Letters. - : American Institute of Physics. - 0003-6951 .- 1077-3118. ; 97:2, s. 023303-
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Tidskriftsartikel (refereegranskat)abstract
- Organic bulk heterojunction (BHJ) solar cells based on a dicyanovinyl-substituted oligothiophene as a donor and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) as an acceptor were fabricated and characterized. The oligothiophene derivative can absorb long wavelength photons of the solar radiation, which makes the solar cells with an optimized weight ratio of 1:1.4 have a decent short-circuit current density (12.4 mA/cm(2)) and open-circuit voltage (0.88 V) under AM 1.5G illumination with an intensity of 100 mW/cm(2). A power conversion efficiency (PCE) of 3.7% is achieved, which is among the best PCEs of solution processed small molecule BHJ solar cells.
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| 9. |
- Yuan, Bo, et al.
(författare)
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Fabrication and microstructure of porous SiC ceramics with Al2O3 and CeO2 as sintering additives
- 2016
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Ingår i: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 42:11, s. 12613-12616
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, porous silicon carbide ceramics were prepared via spark plasma sintering at relatively low temperatures using Al2O3 and CeO2 as sintering additives. Sacrificial template was selected as the pore forming mechanism, and gelcasting was used to fix the slurry in a short time. The evolution process of the microstructures during different steps was observed by SEM. The influence of the sintering temperature and sintering additives on the shrinkage and porosity of the samples was studied. The microstructures of different samples were characterized, and the mechanical properties were also evaluated.
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| 10. |
- Deyev, Sergey M., et al.
(författare)
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Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Metastasis-targeting therapy might improve outcomes in oligometastatic prostate cancer. Epithelial cell adhesion molecule (EpCAM) is overexpressed in 40-60% of prostate cancer cases and might be used as a target for specific delivery of toxins and drugs. Radionuclide molecular imaging could enable non-invasive detection of EpCAM and stratification of patients for targeted therapy. Designed ankyrin repeat proteins (DARPins) are scaffold proteins, which can be selected for specific binding to different targets. The DARPin Ec1 binds strongly to EpCAM. To determine an optimal design of Ec1-based probes, we labeled Ec1 at two different positions with four different nuclides (Ga-68, In-111, Co-57 and I-125) and investigated the impact on Ec1 biodistribution. We found that the C-terminus is the best position for labeling and that In-111 and I-125 provide the best imaging contrast. This study might be helpful for scientists developing imaging probes based on scaffold proteins. The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40-60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [I-125]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1.
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| 11. |
- Garousi, Javad, et al.
(författare)
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Experimental HER2-Targeted Therapy Using ADAPT6-ABD-mcDM1 in Mice Bearing SKOV3 Ovarian Cancer Xenografts : Efficacy and Selection of Companion Imaging Counterpart
- 2022
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:8
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of the human epidermal growth factor receptor 2 (HER2) in breast and gastric cancer is exploited for targeted therapy using monoclonal antibodies and antibody-drug conjugates. Small engineered scaffold proteins, such as the albumin binding domain (ABD) derived affinity proteins (ADAPTs), are a promising new format of targeting probes for development of drug conjugates with well-defined structure and tunable pharmacokinetics. Radiolabeled ADAPT6 has shown excellent tumor-targeting properties in clinical trials. Recently, we developed a drug conjugate based on the HER2-targeting ADAPT6 fused to an albumin binding domain (ABD) for increased bioavailability and conjugated to DM1 for cytotoxic action, designated as ADAPT6-ABD-mcDM1. In this study, we investigated the therapeutic efficacy of this conjugate in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. A secondary aim was to evaluate several formats of imaging probes for visualization of HER2 expression in tumors. Administration of ADAPT6-ABD-mcDM1 provided a significant delay of tumor growth and increased the median survival of the mice, in comparison with both a non-targeting homologous construct (ADAPT(Neg)-ABD-mcDM1) and the vehicle-treated groups, without inducing toxicity to liver or kidneys. Moreover, the evaluation of imaging probes showed that small scaffold proteins, such as Tc-99m(CO)(3)-ADAPT6 or the affibody molecule Tc-99m-Z(HER2:41071), are well suited as diagnostic companions for potential stratification of patients for ADAPT6-ABD-mcDM1-based therapy.
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| 12. |
- Hao, Wenming, et al.
(författare)
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Core-Shell and Hollow Particles of Carbon and SiC Prepared from Hydrochar
- 2019
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- The applications of silicon carbide (SiC) include lightweight materials with thermal shock resistance. In this study, core-shell C-SiC particles were synthesized by compacting and rapidly heating a hydrochar from glucose by using strong pulsed currents and infiltration of silicon vapor. Hollow particles of SiC formed on removing the carbon template. In contrast to related studies, we detected not only the pure 3C polytype (-SiC) but also significant amounts of the 2H or the 6H polytypes (-SiC) in the SiC.
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| 13. |
- Leitao, Charles Dahlsson, et al.
(författare)
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Conditionally activated affibody-based prodrug targeting EGFR demonstrates improved tumor selectivity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Safety and efficacy of cancer-targeting treatments can be improved by conditional activation conferred by the distinct milieu of the tumour microenvironment. Proteases are intricately involved in tumorigenesis and commonly dysregulated with elevated expression and activity. Design of prodrug molecules with protease-dependent activation has the potential to increase tumor-selective targeting, while decreasing the exposure to healthy tissues, thus improving safety, allowing for administration of higher doses or use of more aggressive treatment options, leading to higher therapeutic efficacy. We have previously performed in vitro characterizations of an affibody-based prodrug approach for protease-mediated targeting of EGFR. In this study we demonstrate the potential for selective tumor-targeting and shielded uptake in healthy tissues in vivo using tumor-bearing mice for an EGFR-targeting affibody prodrug.
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| 14. |
- Leitao, Charles Dahlsson, 1992-, et al.
(författare)
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Conditionally activated affibody-based prodrug targeting EGFR demonstrates improved tumour selectivity
- 2023
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 357, s. 185-195
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Tidskriftsartikel (refereegranskat)abstract
- Safety and efficacy of cancer-targeting treatments can be improved by conditional activation enabled by the distinct milieu of the tumour microenvironment. Proteases are intricately involved in tumourigenesis and commonly dysregulated with elevated expression and activity. Design of prodrug molecules with protease -dependent activation has the potential to increase tumour-selective targeting while decreasing exposure to healthy tissues, thus improving the safety profile for patients. Higher selectivity could also allow for adminis-tration of higher doses or use of more aggressive treatment options, leading to higher therapeutic efficacy. We have previously developed an affibody-based prodrug with conditional targeting of EGFR conferred by an anti-idiotypic affibody masking domain (ZB05). We could show that binding to endogenous EGFR on cancer cells in vitro was restored following proteolytic removal of ZB05. In this study we evaluate a novel affibody-based pro -drug design, which incorporates a protease substrate sequence recognized by cancer-associated proteases and demonstrate the potential of this approach for selective tumour-targeting and shielded uptake in healthy tissues in vivo using tumour-bearing mice. This may widen the therapeutic index of cytotoxic EGFR-targeted thera-peutics by decreasing side effects, improving selectivity of drug delivery, and enabling the use of more potent cytotoxic drugs.
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| 15. |
- Liu, Shucheng, et al.
(författare)
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Interface-induced growth of boronate-based metal-organic framework membrane on porous carbon substrate for aqueous phase molecular recognition
- 2017
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Ingår i: Chemical Engineering Journal. - : Elsevier. - 1385-8947 .- 1873-3212. ; 324, s. 216-227
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Tidskriftsartikel (refereegranskat)abstract
- For metal-organic frameworks (MOFs), introduction of special functional groups and integration on porous support will endow the MOF with specific molecular affinity and tunable membrane-like surface properties. Herein, we demonstrated a facile interface-induced Zn(II)-ligand-fragment co-assembly strategy to in situ fabricate boronate-based MOF membrane on hydrophobic porous carbon substrate for specific molecular recognition and separation. Due to the phenylboronic acid groups and hydrophobic porous carbon supporting layer, a catechol-containing medicinal natural flavone Luteolin was found to be efficiently and selectively recognized on the MOF composite in water-containing solution. As compared to the separated MOF particles and carbon substrate, the MOF composite exhibited similar adsorption kinetics but significant higher adsorption capacity in static separation. Dynamic separation also revealed that the MOF composite could achieve a desirable maximum adsorption capacity under mild separation condition, implying its applicability in industrial application. As a proof of this concept, a commercially available Luteolin with 85% purity could be easily extracted and concentrated to 99.90% purity by the MOF composite in highly aqueous solution, and the products possessed the similar antibacterial performance with standard substance. These results demonstrated that, a membrane-like functionalized MOF composite with enhanced surface hydrophobicity and improved molecular specificity has great potential for separation of industrial and even biological samples under water compatible conditions. (C) 2017 Elsevier B. V. All rights reserved.
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| 16. |
- Liu, Yongsheng, et al.
(författare)
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Biologic Evaluation of a Heterodimeric HER2-Albumin Targeted Affibody Molecule Produced by Chemo-Enzymatic Peptide Synthesis
- 2022
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- Targeted molecular radiation therapy is a promising emerging treatment modality in oncology, and peptide synthesis may shorten the time to reach the clinical stage. In this study, we have explored Chemo-Enzymatic Peptide Synthesis, or CEPS, as a new means of producing a therapeutic HER2 targeted Affibody((R)) molecule, comprising a C-terminal albumin binding domain (ABD) for half-life extension and a total length of 108 amino acids. In addition, a DOTA moiety could be incorporated at N-terminus directly during the synthesis step and subsequently utilized for site-specific radiolabeling with the therapeutic radionuclide Lu-177. Retained thermodynamic stability as well as retained binding to both HER2 and albumin was verified. Furthermore, HER2 binding specificity of the radiolabeled Affibody molecule was confirmed by an in vitro saturation assay showing a significantly higher cell-bound activity of SKOV-3 (high HER2 expression) compared with BxPC3 (low HER2 expression), both in the presence and absence of HSA. In vivo evaluation in mice bearing HER2 expressing xenografts also showed specific tumor targeting as well as extended time in circulation and reduced kidney uptake compared with a HER2 targeted Affibody molecule without the ABD moiety. To conclude, we have demonstrated that CEPS can be used for production of Affibody-fusion molecules with retained in vitro and in vivo functionality.
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| 17. |
- Liu, Yongsheng, et al.
(författare)
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Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody® Molecules 177Lu-ABY-271 and 177Lu-ABY-027 : Impact of DOTA Position on ABD Domain
- 2021
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Radiolabeled Affibody-based targeting agent 177Lu-ABY-027, a fusion of an anti-HER2 Affibody molecule with albumin binding domain (ABD) site-specifically labeled at the C-terminus, has demonstrated a promising biodistribution profile in mice; binding of the construct to albumin prevents glomerular filtration and significantly reduces renal uptake. In this study, we tested the hypothesis that site-specific positioning of the chelator at helix 1 of ABD, at a maximum distance from the albumin binding site, would further increase the strength of binding to albumin and decrease the renal uptake. The new construct, ABY-271 with DOTA conjugated at the back of ABD, has been labelled with 177Lu. Targeting properties of 177Lu-ABY-271 and 177Lu-ABY-027 were compared directly. 177Lu-ABY-271 specifically accumulated in SKOV-3 xenografts in mice. The tumor uptake of 177Lu-ABY-271 exceeded uptake in any other organ 24 h and later after injection. However, the renal uptake of 177Lu-ABY-271 was two-fold higher than the uptake of 177Lu-ABY-027. Thus, the placement of chelator on helix 1 of ABD does not provide desirable reduction of renal uptake. To conclude, minimal modification of the design of Affibody molecules has a strong effect on biodistribution, which cannot be predicted a priori. This necessitates extensive structure-properties relationship studies to find an optimal design of Affibody-based targeting agents for therapy.
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| 18. |
- Liu, Yongsheng, et al.
(författare)
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Experimental Therapy of HER2-Expressing Xenografts Using the Second-Generation HER2-Targeting Affibody Molecule 188Re-ZHER2:41071
- 2022
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- HER2-targeted radionuclide therapy might be helpful for the treatment of breast, gastric, and ovarian cancers which have developed resistance to antibody and antibody-drug conjugate-based therapies despite preserved high HER2-expression. Affibody molecules are small targeting proteins based on a non-immunoglobulin scaffold. The goal of this study was to test in an animal model a hypothesis that the second-generation HER2-targeting Affibody molecule 188Re-ZHER2:41071 might be useful for treatment of HER2-expressing malignant tumors. ZHER2:41071 was efficiently labeled with a beta-emitting radionuclide rhenium-188 (188Re). 188Re-ZHER2:41071 demonstrated preserved specificity and high affinity (KD = 5 ± 3 pM) of binding to HER2-expressing cells. In vivo studies demonstrated rapid washout of 188Re from kidneys. The uptake in HER2-expressing SKOV-3 xenografts was HER2-specific and significantly exceeded the renal uptake 4 h after injection and later. The median survival of mice, which were treated by three injections of 16 MBq 188Re-ZHER2:41071 was 68 days, which was significantly longer (<0.0001 in the log-rank Mantel-Cox test) than survival of mice in the control groups treated with vehicle (29 days) or unlabeled ZHER2:41071 (27.5 days). In conclusion, the experimental radionuclide therapy using 188Re-ZHER2:41071 enabled enhancement of survival of mice with human tumors without toxicity to the kidneys, which is the critical organ.
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| 19. |
- Liu, Yongsheng, et al.
(författare)
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Preclinical Evaluation of a New Format of Ga-68- and In-111-Labeled Affibody Molecule Z(IGF-1R:4551) for the Visualization of IGF-1R Expression in Malignant Tumors Using PET and SPECT
- 2022
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- The Insulin-like growth factor-1 receptor (IGF-1R) is a molecular target for several monoclonal antibodies undergoing clinical evaluation as anticancer therapeutics. The non-invasive detection of IGF-1R expression in tumors might enable stratification of patients for specific treatment and improve the outcome of both clinical trials and routine treatment. The affibody molecule Z(IGF-1R:4551) binds specifically to IGF-1R with subnanomolar affinity. The goal of this study was to evaluate the Ga-68 and In-111-labeled affibody construct NODAGA-(HE)(3)-Z(IGF-1R:4551) for the imaging of IGF-1R expression, using PET and SPECT. The labeling was efficient and provided stable coupling of both radionuclides. The two imaging probes, [Ga-68]Ga-NODAGA-(HE)(3)-Z(IGF-1R:4551) and [In-111]In-NODAGA-(HE)(3)-Z(IGF-1R:4551), demonstrated specific binding to IGF-1R-expressing human cancer cell lines in vitro and to IGF-1R-expressing xenografts in mice. Preclinical PET and SPECT/CT imaging demonstrated visualization of IGF-1R-expressing xenografts already one hour after injection. The tumor-to-blood ratios at 3 h after injection were 7.8 +/- 0.2 and 8.0 +/- 0.6 for [Ga-68]Ga-NODAGA-(HE)(3)-Z(IGF-1R:4551) and [In-111]In-NODAGA-(HE)(3)-Z(IGF-1R:4551), respectively. In conclusion, a molecular design of the Z(IGF-1R:4551) affibody molecule, including placement of a (HE)(3)-tag on the N-terminus and site-specific coupling of a NODAGA chelator on the C-terminus, provides a tracer with improved imaging properties for visualization of IGF-1R in malignant tumors, using PET and SPECT.
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| 20. |
- Liu, Yongsheng, et al.
(författare)
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Radionuclide Therapy of HER2-Expressing Xenografts Using [Lu-177]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are artificial proteins that can recognize cancer-related molecular abnormalities in the living body. Clinical studies demonstrated that Affibody molecules can be successfully used for radionuclide diagnostics. Targeted radionuclide therapy selectively delivers cytotoxic radionuclides to malignant tumors, thus sparing normal tissues. For radionuclide therapy, Affibody molecules were re-engineered to decrease accumulation in the kidneys. This study has demonstrated that radionuclide therapy using re-engineered Affibody molecules increases the survival of immunodeficient mice bearing human tumors. The therapy was more efficient than the treatment with a monoclonal antibody, which is currently used in clinical practice. The best results were obtained when both the antibody and radiolabeled Affibody molecules were used simultaneously. This work provides a preclinical rationale for a potentially more efficient treatment in HER2-positive cancers.ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule Z(HER2:2891), which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to Z(HER2:2891) to reduce renal uptake and increase bioavailability. The agent can be site-specifically labeled with a beta-emitting radionuclide Lu-177 using a DOTA chelator. The goals of this study were to test the hypotheses that a targeted radionuclide therapy using [Lu-177]Lu-ABY-027 could extend the survival of mice with HER2-expressing human xenografts and that co-treatment with [Lu-177]Lu-ABY-027 and the HER2-targeting antibody trastuzumab could enhance this effect. Balb/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts were used as in vivo models. A pre-injection of trastuzumab did not reduce the uptake of [Lu-177]Lu-ABY-027 in tumors. Mice were treated with [Lu-177]Lu-ABY-027 or trastuzumab as monotherapies and a combination of these therapies. Mice treated with vehicle or unlabeled ABY-027 were used as controls. Targeted monotherapy using [Lu-177]Lu-ABY-027 improved the survival of mice and was more efficient than trastuzumab monotherapy. A combination of therapies utilizing [Lu-177]Lu-ABY-027 and trastuzumab improved the treatment outcome in comparison with monotherapies using these agents. In conclusion, [Lu-177]Lu-ABY-027 alone or in combination with trastuzumab could be a new potential agent for the treatment of HER2-expressing tumors.
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| 21. |
- Lundmark, Fanny, et al.
(författare)
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Reduction of renal activity retention of radiolabeled albumin binding domain-derived affinity proteins using a non-residualizing label strategy compared with a cleavable glycine-leucine-glycine-lysine-linker
- 2024
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of targeted imaging and therapy using radiolabeled albumin-binding domain-derived affinity proteins (ADAPTs) has been demonstrated. However, high renal uptake of radioactivity limits the maximum tolerated dose. Successful reduction of renal retention of radiolabeled Fab fragments has been demonstrated by incorporating a cleavable linker between the targeting agent and the radiometal chelator. The present study investigated if the introduction of a glycine-leucine-glycine-lysine (GLGK)-linker would reduce the kidney uptake of radiolabeled ADAPT6 and also compared it with the non-residualizing [125I]I-[(4-hydroxyphenyl)ethyl]maleimide ([125I]I-HPEM) labeling strategy. GLGK was site-specifically coupled to human epidermal growth factor receptor 2 (HER2)-targeting ADAPT6. Conjugates without the cleavable linker were used as controls and all constructs were labeled with lutetium-177 (177Lu). [125I]I-HPEM was coupled to ADAPT6 at the C-terminus. Biodistribution of all constructs was evaluated in NMRI mice 4 h after injection. Specific binding to HER2-expressing cells in vitro was demonstrated for all constructs. No significant difference in kidney uptake was observed between the [177Lu]Lu-2,2 ',2",2"'-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid-GLGK-conjugates and the controls. The renal activity of [125I]I-HPEM-ADAPT6 was significantly lower compared with all other constructs. In conclusion, the incorporation of the cleavable GLGK-linker did not result in lower renal retention. Therefore, the present study emphasized that, in order to achieve a reduction of renal retention, alternative molecular design strategies may be required for different targeting agents.
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| 22. |
- Nan, Beiya, et al.
(författare)
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Microstructure and Properties of Porous SiC Ceramics Modified by CVI-SiC Nanowires
- 2019
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Ingår i: Advanced Engineering Materials. - : Wiley. - 1438-1656 .- 1527-2648. ; 21:5
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Tidskriftsartikel (refereegranskat)abstract
- Sintered porous SiC ceramics are modified with SiC nanowires prepared via chemical vapor infiltration (CVI). SiC nanowires are successfully grown within sintered porous SiC ceramics following vapor-liquid-solid growth. The diameter of the SiC nanowires is in the range of 200 nm-1 mu m, and first decreases with increasing input gas ratio (alpha = 50, 60, 70, and 80) and increases thereafter. The diameter of the nanowires decreases from the surface to the interior areas of the porous SiC ceramics. SiC nanowires effectively improve the mechanical properties of the porous SiC ceramics, and sample Ni-50 has the highest flexural strength of 33.91 MPa and fracture toughness of 0.79 MPa center dot m(1/2), which increases by 90.4% and 49.1% compared to an unmodified sample, respectively. Additionally, the presence of SiC nanowires leads to porous SiC ceramics with altered porosity and microstructure, and higher thermal conductivity. The porous SiC ceramics modified by CVI SiC nanowires satisfy the requirements of gas filtration applications and the pressure drop increases with decreasing apparent porosity. The porous SiC ceramics modified with CVI SiC nanowire has higher permeability than those resulting from the introduction of CVI-SiC matrix or CVD-SiC coating into porous SiC ceramics.
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| 23. |
- Nie, Junyang, et al.
(författare)
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Systematic study on size and temporal dependence of micro-LED arrays for display applications
- 2023
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Ingår i: Photonics Research. - 2327-9125. ; 11:4, s. 549-557
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Tidskriftsartikel (refereegranskat)abstract
- Micro-LEDs are one of the most promising candidates for next-generation displays, yet they are inconvenienced by the efficiency reduction induced by the sidewall defects when pursuing further scaled-down device dimensions. We have systematically investigated both the size and temporal dependence of micro-LEDs. Micro-LED arrays with a mesa size ranging from 7 to 100 μm were prepared for display purposes. The luminance and external quantum efficiency (EQE) were measured and discussed. Surprisingly, micro-LED arrays with a smaller mesa size exhibit a higher EQE under 100 ns pulse duration operation when compared with longer pulse duration operations. Under certain short-pulsed excitation, a 7 × 7 μm2 micro-LED array even exhibits a >20% higher EQE as compared to the direct current (DC) or the long duration pulse operation condition.We thus concluded that the notorious efficiency reduction induced by sidewall defects in small-sized micro-LED arrays could be significantly reduced by applying short-pulse voltages.
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| 24. |
- Oroujeni, Maryam, PhD, 1982-, et al.
(författare)
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Affibody-Mediated PNA-Based Pretargeted Cotreatment Improves Survival of Trastuzumab-Treated Mice Bearing HER2-Expressing Xenografts
- 2022
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 63:7, s. 1046-1051
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of patients with human epidermal growth factor receptor 2 (HER2)-expressing tumors using the monoclonal antibody trastuzumab increases survival. The Affibody-based peptide nucleic acid (PNA)-mediated pretargeted radionuclide therapy has demonstrated efficacy against HER2-expressing xenografts in mice. Structural studies suggest that Affibody molecules and trastuzumab bind to different epitopes on HER2. The aim of this study was to test the hypothesis that a combination of PNA-mediated pretargeted radionuclide therapy and trastuzumab treatment of HER2-expressing xenografts can extend survival compared with monotherapies. Methods: Mutual interference of the primary pretargeting probe Z(HER2:342)-SR-HP1 and trastuzumab in binding to HER2-expressing cell lines was investigated in vitro. Experimental therapy evaluated the survival of mice bearing HER2-expressing SKOV-3 xenografts after treatment with vehicle, trastuzumab only, pretargeting using Affibody-PNA chimera Z(HER2:342)-SR-HP1 and complementary probe Lu-177-HP2, and combination of trastuzumab and pretargeting. The ethical permit limited the study to 90 d. The animals'weightsweremonitored during the study. After study termination, samples of liver and kidneys were evaluated by a veterinary pathologist for toxicity signs. Results: The presence of a large molar excess of trastuzumab had no influence on the affinity of Z(HER2:342)-SR-HP1 binding to HER2-expressing cells in vitro. The affinity of trastuzumab was not affected by a large excess of Z(HER2:342)-SR-HP1. Themedian survival of mice treated with trastuzumab (75.5 d) was significantly longer than the survival of mice treated with a vehicle (59.5 d). Median survival of mice treated with pretargeting was not reached by day 90. Six mice of 10 in this group survived, and 2 had complete remission. All mice in the combination treatment group survived, and tumors in 7 mice had disappeared at study termination. There was no significant difference between animal weights in the different treatment groups. No significant pathologic alterations were detected in livers and kidneys of treated animals. Conclusion: Treatment of mice bearing HER2-expressing xenografts with the combination of trastuzumab and Affibody-mediated PNA-based radionuclide pretargeting significantly increased survival compared with monotherapies. Cotreatment was not toxic for normal tissues.
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| 25. |
- Oroujeni, Maryam, PhD, 1982-, et al.
(författare)
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Evaluation of affinity matured Affibody molecules for imaging of the immune checkpoint protein B7-H3
- 2023
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 124-125
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Tidskriftsartikel (refereegranskat)abstract
- B7-H3 (CD276), an immune checkpoint protein, is a promising molecular target for immune therapy of malignant tumours. Sufficient B7-H3 expression level is a precondition for successful therapy. Radionuclide molecular imaging is a powerful technique for visualization of expression levels of molecular targets in vivo. Use of small radiolabelled targeting proteins would enable high-contrast radionuclide imaging of molecular targets if adequate binding affinity and specificity of an imaging probe could be provided. Affibody molecules, small engineered affinity proteins based on a non-immunoglobulin scaffold, have demonstrated an appreciable potential in radionuclide imaging. Proof-of principle of radionuclide visualization of expression levels of B7-H3 in vivo was demonstrated using the [99mTc]Tc-AC12-GGGC Affibody molecule. We performed an affinity maturation of AC12, enabling selection of clones with higher affinity. Three most promising clones were expressed with a -GGGC (triglycine-cysteine) chelating sequence at the C-terminus and labelled with technetium-99m (99mTc). 99mTc-labelled conjugates bound to B7-H3-expressing cells specifically in vitro and in vivo. Biodistribution in mice bearing B7-H3-expressing SKOV-3 xenografts demonstrated improved imaging properties of the new conjugates compared with the parental variant [99mTc]Tc-AC12-GGGC. [99mTc]Tc-SYNT-179 provided the strongest improvement of tumour-to-organ ratios. Thus, affinity maturation of B7-H3 Affibody molecules could improve biodistribution and targeting properties for imaging of B7-H3-expressing tumours.
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| 26. |
- Oroujeni, Maryam, PhD, 1982-, et al.
(författare)
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Evaluation of an Affibody-Based Binder for Imaging of Immune Check-Point Molecule B7-H3
- 2022
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Radionuclide molecular imaging could provide an accurate assessment of the expression of molecular targets in disseminated cancers enabling stratification of patients for specific therapies. B7-H3 (CD276) is a transmembrane protein belonging to the B7 superfamily. This protein is overexpressed in different types of human malignancies and such upregulation is generally associated with a poor clinical prognosis. In this study, targeting properties of an Affibody-based probe, AC12, containing a -GGGC amino acid sequence as a chelator (designated as AC12-GGGC) labelled with technetium-99m (Tc-99m) were evaluated for imaging of B7-H3-expressing tumours. AC12-GGGC was efficiently labelled with Tc-99m. [Tc-99m]Tc-AC12-GGGC bound specifically to B7-H3 expressing cells in vitro with affinities in nanomolar range. In mice bearing B7-H3-expressing xenografts, [Tc-99m]Tc-AC12-GGGC showed tumour uptake of 2.1 +/- 0.5 %ID/g at 2 h after injection. Its clearance from blood, normal organs and tissues was very rapid. This new targeting agent, [Tc-99m]Tc-AC12-GGGC, provided high tumour-to-blood ratio already at 2 h (8.2 +/- 1.9), which increased to 11.0 +/- 0.5 at 4 h after injection. Significantly (p < 0.05) higher tumour-to-liver and higher tumour-to-bone ratios at 2 h in comparison with 4 h after injection were observed. Thus, [Tc-99m]Tc-AC12-GGGC could be a promising candidate for further development.
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| 27. |
- Tano, Hanna, et al.
(författare)
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Comparative Evaluation of Novel Lu-177-Labeled PNA Probes for Affibody-Mediated PNA-Based Pretargeting
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Affibody molecules are small, engineered affinity proteins based on a nonimmunoglobulin scaffold. Affibody-based radionuclide imaging probes have demonstrated excellent tumor targeting. However, the renal clearance of affibody molecules is accompanied by high reabsorption and retention of activity in the kidney, which prevents their use for radionuclide therapy. We have previously shown the feasibility of overcoming the high renal uptake using a pretargeting approach for affibody-mediated therapy based on peptide nucleic acid (PNA) hybridization. In this study, we test the hypothesis that shortening the PNA pretargeting probes would further increase the difference between the accumulation of radiometals in tumor xenografts and in kidneys. A series of novel PNA probes has been designed and evaluated in vitro and in vivo. We have found that a variant containing 9 nucleobases enables a two-fold increase of the tumor-to-kidney dose ratio compared with a variant containing 15 nucleobases. This creates preconditions for more efficient therapy of cancer. Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening the PNA pretargeting probes would increase the tumor-to-kidney dose ratio. The primary probe Z(HER2:342)-SR-HP15 and the complementary secondary probes HP16, HP17, and HP18, containing 9, 12, and 15 nucleobases, respectively, and carrying a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, synthesized, characterized in vitro, and labeled with Lu-177. In vitro pretargeting was studied in HER2-expressing SKOV3 and BT474 cell lines. The biodistribution of these novel probes was evaluated in immunodeficient mice bearing SKOV3 xenografts and compared to the previously studied [Lu-177]Lu-HP2. Characterization confirmed the formation of high-affinity duplexes between HP15 and the secondary probes, with the affinity correlating with the length of the complementary PNA sequences. All the PNA-based probes were bound specifically to HER2-expressing cells in vitro. In vivo studies demonstrated HER2-specific uptake of all Lu-177-labeled probes in xenografts in a pretargeting setting. The ratio of cumulated radioactivity in the tumor to the radioactivity in kidneys was dependent on the secondary probe's size and decreased with an increased number of nucleobases. The shortest PNA probe, [Lu-177]Lu-HP16, showed the highest tumor-to-kidney ratio. [Lu-177]Lu-HP16 is the most promising secondary probe for affibody-mediated tumor pretargeting.
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| 28. |
- Vorobyeva, Anzhelika, et al.
(författare)
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Investigation of a Pharmacological Approach for Reduction of Renal Uptake of Radiolabeled ADAPT Scaffold Protein
- 2020
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:19
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Tidskriftsartikel (refereegranskat)abstract
- Albumin binding domain-Derived Affinity ProTeins (ADAPTs) are small (5 kDa) engineered scaffold proteins that are promising targeting agents for radionuclide-based imaging. A recent clinical study has demonstrated that radiolabeled ADAPTs can efficiently visualize human epidermal growth factor receptor 2 (HER2) expression in breast cancer using SPECT imaging. However, the use of ADAPTs directly labeled with radiometals for targeted radionuclide therapy is limited by their high reabsorption and prolonged retention of activity in kidneys. In this study, we investigated whether a co-injection of lysine or gelofusin, commonly used for reduction of renal uptake of radiolabeled peptides in clinics, would reduce the renal uptake of [Tc-99m]Tc(CO)(3)-ADAPT6 in NMRI mice. In order to better understand the mechanism behind the reabsorption of [Tc-99m]Tc(CO)(3)-ADAPT6, we included several compounds that act on various parts of the reabsorption system in kidneys. Administration of gelofusine, lysine, probenecid, furosemide, mannitol, or colchicine did not change the uptake of [Tc-99m]Tc(CO)(3)-ADAPT6 in kidneys. Sodium maleate reduced the uptake of [Tc-99m]Tc(CO)(3)-ADAPT6 to ca. 25% of the uptake in the control, a high dose of fructose (50 mmol/kg) reduced the uptake by ca. two-fold. However, a lower dose (20 mmol/kg) had no effect. These results indicate that common clinical strategies are not effective for reduction of kidney uptake of [Tc-99m]Tc(CO)(3)-ADAPT6 and that other strategies for reduction of activity uptake or retention in kidneys should be investigated for ADAPT6.
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| 29. |
- Xu, Tianqi, et al.
(författare)
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Epithelial cell adhesion molecule-targeting designed ankyrin repeat protein-toxin fusion Ec1-LoPE exhibits potent cytotoxic action in prostate cancer cells
- 2022
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 47:5
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Tidskriftsartikel (refereegranskat)abstract
- Targeted anticancer therapeutics offer the advantage of reducing cytotoxic side effects to normal cells by directing the cytotoxic payload selectively to cancer cells. Designed ankyrin repeat proteins (DARPins) are promising non-immunoglobulin-based scaffold proteins for payload delivery to cancer-associated molecular targets. Epithelial cell adhesion molecule (EpCAM) is overexpressed in 40-60% of prostate cancers (PCs) and is associated with metastasis, increased risk of PC recurrence and resistance to treatment. Here, we investigated the use of DARPin Ec1 for targeted delivery of Pseudomonas exotoxin A variant (LoPE) with low immunogenicity and low non-specific toxicity to EpCAM-expressing prostate cancer cells. Ec1-LoPE fusion protein was radiolabeled with tricarbonyl technetium-99m and its binding specificity, binding kinetics, cellular processing, internalization and cytotoxicity were evaluated in PC-3 and DU145 cell lines. Ec1-LoPE showed EpCAM-specific binding to EpCAM-expressing prostate cancer cells. Rapid internalization mediated potent cytotoxic effect with picomolar IC50 values in both studied cell lines. Taken together, these data support further evaluation of Ec1-LoPE in a therapeutic setting in a prostate cancer model in vivo.
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| 30. |
- Yin, Wen, 1993-, et al.
(författare)
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A comparison of affibody conjugates loaded with auristatin and maytansine derived drugs
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Auristatin and maytansine-derived drugs are cytotoxic tubulin polymerization inhibitors commonly used as payloads in drug conjugates intended for targeted cancer therapy. We have previously shown that an affibody molecule ZHER2, binding to the human epidermal growth factor receptor 2 (HER2), can be site-specifically conjugated to DM1, a maytansine- derived payload, creating the potent and specific drug conjugate, ZHER2-ABD-mcDM1, where the ABD is an albumin binding domain used for in vivo half-life extension. Here, we investigated the properties of the HER2-binding affibody molecule conjugated with the two auristatin-derived payloads, monomethyl auristatin E and F (MMAE and MMAF), in comparison with the construct with DM1. We found that the drug conjugate ZHER2-ABD- mcMMAF was more potent than ZHER2-ABD-mcDM1, with IC50 values to high-HER2 expressing cell lines ranging from 0.18 to 12 nM. By contrast the IC50 values of ZHER2-ABD- mcMMAE was considerably weaker and this construct would probably benefit from a different linker connecting the drug to the affibody fusion protein. Quantification of uptake in HER2-expressing tumors and normal organs of 99m-technetium labeled drug conjugates showed that they were predominantly cleared by the kidneys, with relatively high tumor uptake, peaking at 11.1 ± 4.1 %ID/g for ZHER2-ABD-mcMMAE at 24 h post-injection, 8.5 ± 1.5 %ID/g for ZHER2-ABD-mcMMAF at 48 h post-injection, and 7.1 ± 1.8 %ID/g for ZHER2- ABD-mcDM1 at 48 h post-injection. Most normal organs, except for the kidneys, had a relatively low uptake. In conclusion, ZHER2-ABD-mcMMAF was the best performing drug conjugate with the highest potency, and lowest uptake in liver; slightly outperforming ZHER2- ABD-mcDM1.
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| 31. |
- Yin, Wen, 1993-, et al.
(författare)
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Comparison of HER2-targeted affibody conjugates loaded with auristatin-and maytansine-derived drugs
- 2023
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 355, s. 515-527
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with antibody drug conjugates targeting receptors over-expressed on cancer cells is well established for clinical use in several types of cancer, however, resistance often occurs motivating the development of novel drugs. We have recently investigated a drug conjugate consisting of an affibody molecule targeting the human epidermal growth factor receptor 2 (HER2), fused to an albumin-binding domain (ABD) for half-life extension, loaded with the cytotoxic maytansine derivative DM1. In this study, we investigated the impact of the cytotoxic payload on binding properties, cytotoxicity and biodistribution by comparing DM1 with the auristatins MMAE and MMAF, as part of the drug conjugate. All constructs had specific and high affinity binding to HER2, human and mouse albumins with values in the low- to sub-nM range. ZHER2-ABD-mcMMAF demonstrated the most potent cytotoxic effect on several HER2-over-expressing cell lines. In an experimental therapy study, the MMAFbased conjugate provided complete tumor regression in 50% of BALB/c nu/nu mice bearing HER2-overexpressing SKOV3 tumors at a 2.9 mg/kg dose, while the same dose of ZHER2-ABD-mcDM1 provided only a moderate anti-tumor effect. A comparison with the non-targeting ZTaq-ABD-mcMMAF control demonstrated HER2-targeting specificity. In conclusion, a combination of potent cytotoxicity in vitro, with minimal uptake in normal organs in vivo, and efficient delivery to tumors provided a superior anti-tumor effect of ZHER2-ABDmcMMAF, while maintaining a favorable toxicity profile with no observed adverse effects.
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| 32. |
- You, Qiangwei, et al.
(författare)
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Microstructure and properties of porous SiC ceramics by LPCVI technique regulation
- 2017
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Ingår i: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 43:15, s. 11855-11863
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Tidskriftsartikel (refereegranskat)abstract
- A new gradient pore structure in porous SiC ceramics was fabricated by low pressure chemical vapor infiltration (LPCVI). Effects of deposition duration on the mechanical properties and permeability of porous SiC ceramics were investigated. Results demonstrated that pore diameter and shapes decreased from the surface to the interior along with LPCVI duration. Porous SiC ceramics with deposition duration of 160 h exhibited flexural strength of 48.05 MPa and fracture toughness of 1.30 MPa m(1/2), where 221% and 189% improvements were obtained compared to porous SiC ceramics without LPCVI, due to CVI-SiC layer strengthening effect. Additionally, at the same gas velocity, pressure drop increase rate was faster due to apparent porosity and pore size change.
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| 33. |
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| 34. |
- Zhang, Jiangbin, et al.
(författare)
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Efficient non-fullerene organic solar cells employing sequentially deposited donor-acceptor layers
- 2018
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Ingår i: Journal of Materials Chemistry A. - : ROYAL SOC CHEMISTRY. - 2050-7488 .- 2050-7496. ; 6:37, s. 18225-18233
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Tidskriftsartikel (refereegranskat)abstract
- Non-fullerene acceptors (NFAs) have recently outperformed their fullerene counterparts in binary bulk-heterojunction (BHJ) organic solar cells (OSCs). Further development of NFA OSCs may benefit other novel OSC device structures that alter or extend the standard BHJ concept. Here, we report such a new processing route that forms a BHJ-like morphology between sequentially processed polymer donor and NFA with high power conversion efficiencies in excess of 10%. Both devices show similar charge generation and recombination behaviours, supporting formation of similar BHJ active layers. We correlate the approximate to 30 meV smaller open-circuit voltage in sq-BHJ devices to more substantial non-radiative recombination by voltage loss analysis. We also determine the exciton diffusion length of benchmark polymer PBDB-T to be 10 +/- 3 nm. Our results demonstrate high-efficiency OSC devices using sequential deposition method and provide new opportunities to further improve performance of state-of-the-art OSCs.
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