| 1. |
- Asem, Heba, et al.
(författare)
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Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging
- 2016
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Ingår i: Journal of Nanobiotechnology. - : BioMed Central (BMC). - 1477-3155. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multifunctional nanocarriers for controlled drug delivery, imaging of disease development and follow-up of treatment efficacy are promising novel tools for disease diagnosis and treatment. In the current investigation, we present a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as a model for lipophilic antineoplastic drugs were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) micelles via the emulsion-evaporation method, and PEG-PCL was labelled with VivoTag 680XL fluorochrome for in vivo fluorescence imaging. Results: Busulphan entrapment efficiency was 83% while the drug release showed a sustained pattern over 10 h. SPION loaded-PEG-PCL micelles showed contrast enhancement in T-2*-weighted MRI with high r(2)* relaxivity. In vitro cellular uptake of PEG-PCL micelles labeled with fluorescein in J774A cells was found to be time-dependent. The maximum uptake was observed after 24 h of incubation. The biodistribution of PEG-PCL micelles functionalized with VivoTag 680XL was investigated in Balb/c mice over 48 h using in vivo fluorescence imaging. The results of real-time live imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL micelles were highly distributed into the lungs during the first 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h post administration. No pathological impairment was found in the major organs studied. Conclusions: Thus, with loaded contrast agent and conjugated fluorochrome, PEG-PCL micelles as biodegradable and biocompatible nanocarriers are efficient multimodal imaging agents, offering high drug loading capacity, and sustained drug release. These might offer high treatment efficacy and real-time tracking of the drug delivery system in vivo, which is crucial for designing of an efficient drug delivery system.
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| 2. |
- Bhattacharya, Kunal, et al.
(författare)
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Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
- 2014
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 6:24, s. 14686-14690
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Tidskriftsartikel (refereegranskat)abstract
- Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising-and degradable-nanomedicine vector.
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| 3. |
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| 4. |
- Eita, Mohamed, et al.
(författare)
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Optical properties of thin films of zinc oxide quantum dots and polydimethylsiloxane : UV-blocking and the effect of cross-linking
- 2012
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 387, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Thin films of polydimethylsiloxane (PDMS) and ZnO quantum dots (QDs) were built up as multilayers by spin-coating. The films are characterized by a UV-blocking ability that increases with increasing number of bilayers. Photoluminescence (PL) emission spectra of the thin films occur at 522 nm, which is the PL wavelength of the ZnO QDs dispersion, but with a lower intensity and a quantum yield (QY) less than 1% that of the dispersion. Cross-linking has introduced new features to the absorption spectra in that the absorption peak was absent. These changes were attributed to the morphological and structural changes revealed by transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR), respectively. TEM showed that the ZnO particle size in the film increased from 7 (+/- 2.7) nm to 16 (+/- 7.8) upon cross-linking. The FTIR spectra suggest that ZnO QDs are involved in the cross-linking of PDMS and that the surface of the ZnO QDs has been chemically modified.
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| 5. |
- El-Sayed, Ramy
(författare)
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Carbon nanotubes in nanomedicine
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of nanomedicine is based primarily on the development of smart and multifunctional nanomaterials that can serve under the different clusters including drug delivery systems, diagnostics, and regenerative medicine. Recently, carbon nanotubes (CNTs) have received enormous attention due to their extraordinary properties. CNTs have a wide range of applications and are used in a variety of products thus exposure to CNTs has become unavoidable, which may prompt an inflammatory response. The present Thesis is focused on studying CNTs especially addressing the key challenges highlighted by the Food and Drug Administration and the Alliance for Nano-Health, including imaging, biodistribution, interaction with biological environment, and predictive modeling. For imaging in order to evaluate biodistribution we were able, for the first time, to use thermostable Luciferase from Luciola cruciate (LcL) as a qualitative imaging modality. LcL offers an alternative approach for following the biodistribution of CNTs over time. The biodistribution profile of CNTs was found to be similar to the majority of nanoparticles, falling in the same size criteria, and predominantly accumulate in the liver. This raised the question whether CNTs could interfere with the liver functionality explicitly the metabolizing activity of drugs and other xenobiotics by phase I metabolizing enzymes CYP450. We therefore studied the ability of single wall carbon nanotubes (oxSWNTs) on inhibiting enzymatic capacity of CYP3A4. We found that oxSWNTs inhibit mediated conversion of testosterone (as a model compound), to its major metabolite 6β-hydroxy testosterone in a dose dependent manner. When oxSWNTs is pre-coated with bovine serum albumin, the enzymatic activity of CYP3A4 was restored. Also, the covalent functionalization of oxSWNTs with polyethylene glycol (PEG) has shown to have no influence on the enzymatic activity of CYP3A4. Further understanding of the molecular interactions was obtained by computational modeling and simulations (MD). MD simulations revealed that the inhibition of CYP3A4 catalytic activity is mainly due to blocking of the exit channel for substrate/products through a complex binding mechanism. CYP3A4 is a well-recognized isozyme accountable for the metabolization of various endogenous and exogenous xenobiotics by means of the monooxygenase cycle. In the Thesis, we also studied the degradation of pristine and oxidized SWNTs (p-SWNTs, oxSWNTs) by CYP3A4, by Raman spectroscopy. We found that both p-SWNTs and oxSWNTs were degraded as evidenced by the increase of D-band, which corresponds to the increase of the structural defects. Surprisingly, CYP3A4 bactosomes were more proficient in degrading p-SWNTs more than oxSWNTs under similar incubation conditions. MD simulations suggested that CYP3A4 has a higher affinity for p-SWNTs (minimal MolDock Score of −186.34 kcal/mol) compared to oxSWNTs which bind in a weaker manner (MolDock Score = −111.47 kcal/mol). Pulmonary accumulation of CNTs has shown to be critical. We therefore studied the biodegradation of oxSWNTs by Lactoperoxidase (LPO), a secreted peroxidase enzyme present in the mucus of the airways. We also investigated whether pulmonary surfactants can play a role in the biodegradation of oxSWNTs. Biodegradation was monitored using Raman spectroscopy, scanning electron microscopy, and UV–Vis–NIR spectroscopy. The biodegradation of oxSWNTs was not impeded by the formation of protein corona formed in the presence of lung surfactant (Curosurf®). Moreover, cell-free digestion of oxSWNTs was observed ex vivo in murine bronchoalveolar lavage fluid in the presence of peroxidase cofactors. Since CNTs is studied as a theranostic agent, we therefore studied the biodegradation of PEGylated oxSWNTs. PEG is acknowledged as the gold standard for extending blood circulation times for many biological molecules. OxSWNTs functionalized with PEG of different molecular weight (MW) were incubated with myeloperoxidase (MPO). Biodegradation was noted only for oxSWNTs chemically functionalized with PEG. There was no sign of degradation of oxSWNTs with physically adsorbed PEG, nor for p-SWNTs. The extent of oxSWNT biodegradation by MPO was inversely proportional to the molecular weight of the PEG chains. Ex vivo biodegradation using isolated primary human neutrophils revealed that both chemically and physically PEGylated oxSWNTs undergo biodegradation independently of the PEG chain MW. These ex vivo findings suggest that, in a cell system, a combined process of stripping and biodegradation of PEGylated oxSWNTs might occur.
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| 6. |
- El-Sayed, Ramy, et al.
(författare)
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Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- We report a detailed computational and experimental study of the interaction of single-walled carbon nanotubes (SWCNTs) with the drug-metabolizing cytochrome P450 enzyme, CYP3A4. Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6 beta-hydroxy testosterone was noted. Evidence for a direct interaction between SWCNTs and CYP3A4 was also provided. The inhibition of enzyme activity was alleviated when SWCNTs were pre-coated with bovine serum albumin. Furthermore, covalent functionalization of SWCNTs with polyethylene glycol (PEG) chains mitigated the inhibition of CYP3A4 enzymatic activity. Molecular dynamics simulations suggested that inhibition of the catalytic activity of CYP3A4 is mainly due to blocking of the exit channel for substrates/products through a complex binding mechanism. This work suggests that SWCNTs could interfere with metabolism of drugs and other xenobiotics and provides a molecular mechanism for this toxicity. Our study also suggests means to reduce this toxicity, eg., by surface modification.
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| 7. |
- El-Sayed, Ramy, et al.
(författare)
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Thermostable Luciferase from Luciola cruciate for Imaging of Carbon Nanotubes and Carbon Nanotubes Carrying Doxorubicin Using in Vivo Imaging System
- 2013
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 13:4, s. 1393-1398
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we introduce a novel method for in vivo imaging of the biodistribution of single wall carbon nanotubes (SWNTs) labeled with recombinant thermo-stable Luciola cruciata luciferase (LcL). In addition, we highlight a new application for green fluorescent proteins in which they are utilized as imaging moieties for SWNTs. Carbon nanotubes show great positive potential compared to other drug nanocarriers with respect to loading capacity, cell internalization, and biodegradability. We have also studied the effect of binding mode (chemical conjugation and physical adsorption) on the chemiluminescence activity, decay rate, and half-life. We have shown that through proper chemical conjugation of LcL to CNTs, LcL remained biologically active for the catalysis of D-luciferin in the presence of ATP to release detectable amounts of photons for in vivo imaging. Chemiluminescence of LcL allows imaging of CNTs and their cargo in nonsuperficial locations at an organ resolution with no need of an excitation source. Loading LcL-CNTs with the antitumor antibiotic doxorubicin did not alter their biological activity for imaging. In vivo imaging of LcL-CNTs has been carried out using "IVIS spectrum" showing the uptake of LcL-CNTs by different organs in mice. We believe that the LcL-CNT system is an advanced powerful tool for in vivo imaging and therefore a step toward the advancement of the nanomellicine field.
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| 8. |
- Shahid, Robina, et al.
(författare)
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Microwave assisted synthesis of ZnS quantum dots using ionic liquids
- 2012
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Ingår i: Materials letters (General ed.). - : Elsevier BV. - 0167-577X .- 1873-4979. ; 89, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- In this work we report results from microwave (MW) assisted synthesis of highly crystalline ZnS quantum dots (QDs) using ionic liquid (ILs) as MW absorbing medium. Two types of ionic liquids, imidazolium and phosphonium based, were used. The QDs are less than 5 nm in size and of wurtzite ZnS type, as characterized by high-resolution transmission electron microscopy (HR-TEM) and selected area electron diffraction (SAED) pattern. The optical properties were investigated by UV-vis absorption and show a blue shift in absorption as compared to bulk wurtzite ZnS due to quantum confinement effects. The photoluminescence (PL) spectra of the QDs show different trap state emissions.
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| 9. |
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| 10. |
- Zhao, Ying, et al.
(författare)
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Multimodal Imaging of Pancreatic Ductal Adenocarcinoma Using Multifunctional Nanoparticles as Contrast Agents
- 2020
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 12:48, s. 53665-53681
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Tidskriftsartikel (refereegranskat)abstract
- Late diagnosis and refractory behavior toward current treatment protocols make pancreatic ductal adenocarcinoma (PDAC) one of the most difficult cancer forms to treat. The imaging-based approach plays an important role to identify potentially curable PDAC patients in high-risk groups at the early stage. In the present study, we developed a core-shell structured gold nanorod (AuNR) as a contrast agent for multimodal imaging and investigated its application for PDAC diagnosis. The composite nanopartides composed of a AuNR core inside a layer of mesoporous silica that was then coated with a gadolinium oxide carbonate shell (AuNR-SiO2 -Gd) are designed to be used in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and photoacoustic imaging (PM). A phantom study with the AuNR-SiO2-Gd NPs demonstrated higher MRI contrast compared to Gadovist and higher X-ray attenuation than Visipaque. A strong, stable, and broad wavelength range signal with a peak at 800 nm was observed in PAI. The AuNR-SiO2-Gd NPs showed significant contrast enhancement under PAI/MRI/CT in both the liver and spleen of control mice after intravenous administration. The utility in PDAC was studied in a genetically engineered mouse model carrying Kras and p53 mutations, which develops spontaneous tumors and keeps the desmoplasia and hypovascularity feature of PDAC in patients. The AuNR-SiO2-Gd NPs were highly accumulated in the surrounding soft tissues but were sparsely distributed throughout the tumor due to dense stroma infiltration and poor tumor vascularization. Hence, a negative contrast within the tumor area in CT/PAI and a positive contrast in MRI were observed. In conclusion, AuNR-SiO2-Gd NPs have good potential to be developed as a multimodal contrast agent for PDAC, which might improve early diagnosis and benefit the clinical outcome for PDAC patients.
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