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- Parakhonskiy, Bogdan, V, et al.
(författare)
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A method of drug delivery to tumors based on rapidly biodegradable drug-loaded containers
- 2021
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Ingår i: APPLIED MATERIALS TODAY. - : Elsevier. - 2352-9407. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- To mitigate side effects in systemic administration, anticancer drugs are encapuslated in nanocontainers. The nanocontainers are impermeable through normal vessel walls but can permeate and retain in the tumor, albeit their diffusive transport in the tumor interstitium towards pharmacological targets is drastically hindered by the tumor microenvironment resulting in a compromised therapeutic efficacy. We introduce a new drug delivery concept, which relies on drug container passive accumulation in the tumor vasculature followed by an hours-scale release of small-molecule payload that cross the capillary walls to the tumor interstitium and permeates the tumor parenchyma. To demonstrate this approach, a colloidal solution of geology-inspired sub-micron vaterite particles (VPs) loaded with photosensitiser drug porphyrazine was used to deliver and visualise porphyrazine biodistribution in the tumors in vivo . The tumor uptake of polyethylene-glycol-coated gold nanorods and porphyrazine was enhanced c.a 4-fold and 1.8-fold, respectively, when formulated in VP containers. The tumor uptake of similar to 30%ID/g much higher than the field average was achieved and enabled successful photodynamic therapy.
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| 2. |
- Pridatchenko, L, et al.
(författare)
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Use of models of biomacromolecule separation in AMT database generation for shotgun proteomics
- 2009
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Ingår i: Biochemistry (Moscow). - 0006-2979 .- 1608-3040. ; 74:11, s. 1195-1202
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Tidskriftsartikel (refereegranskat)abstract
- Generation of a complex proteome database requires use of powerful analytical methods capable of following rapid changes in the proteome due to changing physiological and pathological states of the organism under study. One of the promising technologies with this regard is the use of so-called Accurate Mass and Time (AMT) tag peptide databases. Generation of an AMT database for a complex proteome requires combined efforts by many research groups and laboratories, but the chromatography data resulting from these efforts are tied to the particular experimental conditions and, in general, are not transferable from one platform to another. In this work, we consider an approach to solve this problem that is based on the generation of a universal scale for the chromatography data using a multiple-point normalization method. The method follows from the concept of linear correlation between chromatography data obtained over a wide range of separation parameters. The method is further tested for tryptic peptide mixtures with experimental data collected from mutual studies by different independent research groups using different separation protocols and mass spectrometry data processing tools.
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| 5. |
- Bragina, O. D., et al.
(författare)
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A direct comparison of the diagnostic efficacy of alternative scaffold- based radiopharmaceuticals [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 in patients with HER2-positive breast cancer
- 2023
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Ingår i: BYULLETEN SIBIRSKOY MEDITSINY. - 1682-0363 .- 1819-3684. ; 22:3, s. 6-13
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Tidskriftsartikel (refereegranskat)abstract
- Aim. To perform a direct comparison of the diagnostic efficacy of [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 in HER2-positive breast cancer patients before the systemic treatment.Materials and methods. The study included 11 patients with HER2-positive breast cancer (T1-4N0-2M0-1) before the initiation of systemic treatment. All patients underwent a radionuclide examination with [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 with the interval of 3-4 days. Single-photon emission computed tomography (SPECT) /computed tomography (CT) was performed 2 and 4 hours after [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 administration, respectively.Results. The analysis of [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 distribution showed their high uptake in the kidneys and liver. Breast tumors were visualized in all cases. The average tumor uptake of [(99)mTc]Tc-ADAPT6 was 4.7 +/- 2.1, which was significantly higher than in the [(99)mTc]Tc-(HE)3-G3 injection (3.5 +/- 1.7) (p < 0.005, paired t-test). The tumor-to-background ratio (15.2 +/- 7.4 and 19.6 +/- 12.4, respectively) had no statistical differences in both cases (p > 0.05, paired t -test). Liver metastases were visualized in patients 1 and 5 and corresponded to the projection of metastases according to contrast-enhanced abdominal CT. The accumulation of [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 in the projection of metastases in both cases was significantly higher compared to the primary tumor (1.3 and 1.7 times higher in patient 1; 2.2 and 3.5 times higher in patient 5, respectively).Conclusion. Both [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 demonstrated the diagnostic efficacy in visualizing a primary HER2-positive tumor in breast cancer patients. However, [(99)mTc]Tc-ADEPT6 had higher accumulation values, which makes it a more promising diagnostic agent.
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| 6. |
- Bragina, O. D., et al.
(författare)
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Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules : the first experience of clinical use
- 2021
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Ingår i: Bûlleten' sibirskoj mediciny. - : Siberian State Medical University. - 1682-0363 .- 1819-3684. ; 20:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Background. The main purpose of the Her2/neu status determination in clinical practice is to determine the indications for the appointment of targeted therapy. The main methods for detecting the Her2/neu status are the immunohistochemical method (IHC) and the fluorescence in situ hybridization (FISH); however, despite their widespread use, they have a number of significant disadvantages. Over the past few years, radionuclide diagnostics using a new class of alternative scaffold proteins that meet all the requirements for optimal delivery of radionuclides to tumor cells has become widespread.Aim. To study the possibility of clinical use of a radiopharmaceutical based on technetium-99m-labeled target molecules for the diagnosis of breast cancer with the Her2/neu overexpression in humans.Materials and methods. The study included 11 patients with breast cancer (T1–4N0–2M0) before systemic therapy: 5 with Her2/neu overexpression; expression of the marker was not detected in 6. In all cases, morphologicaland immunohistochemical studies were performed. In case of Her2/neu 2+, FISH analysis was performed. The radiopharmaceutical was prepared immediately before administration, after which it was slowly injected intravenously into the patient. Scintigraphic studies in the “WholeBody” mode and SPECT of the chest organs were performed 2, 4, 6 and 24 hours after injection.Results. Radiochemical yield, radiochemical purity and activity before administration were (80 ± 4)%, (98 ± 1)% and (434 ± 19.5) MBq, respectively. The greatest uptake by normal organs was observed at a time interval of 6 hours in the kidneys and at a moderate activity in the liver and lungs at the same time interval. The organ with the highest absorbed dose was the kidneys; significant accumulation was also detected in the adrenal glands, gallbladder, liver, pancreas and spleen. The smallest accu mulation of the studied drug was observed in the brain (0.001 ± 0.000) mGy and skin (0.001 ± 0.000) mGy. The effective dose was (0.009 ± 0.002) mGy. The difference between tumors with positive and negative Her2-neu expression was found at all time points. In this case, the best indicator was determined after 2 hours of drug injection (р < 0.05).Conclusion. Based on the results obtained, it can be indicated that the investigated radiopharmaceutical can be considered as a new additional method for the diagnosis of Her2-positive breast tumors.
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