International journal of nanomedicine · 2026
Bevacizumab-Functionalized Exosome-Associated Chitosan Nanocomposite for Temozolomide Delivery and Apoptosis-Related Transcriptional Modulation in Experimental Glioma.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Pourmasoumi Parvin, Zamani Farshid, Bayat Mohammad, Amini Abdollah
Аннотация
INTRODUCTION: Glioblastoma (GBM) has a poor prognosis, and temozolomide (TMZ) therapy is limited by a short half-life and insufficient intratumoral availability. We developed a bevacizumab (BVZ)-functionalized, exosome-associated chitosan nanocomposite loaded with TMZ (BVZ-Exo@CS-TMZ) as a multifunctional biohybrid platform for experimental glioma therapy.
METHODS: CS-TMZ nanoparticles were prepared by ionotropic gelation, non-covalently associated with adipose-derived stromal cell exosomes (Exo), and functionalized with BVZ via EDC/NHS conjugation to accessible surface carboxyl groups. The Exo preparation was characterized by Western blotting, while the final formulation was characterized by FTIR, XRD, FESEM, TEM, DLS, zeta potential, and VEGF-binding ELISA. Apparent TMZ retention, loading, and release were quantified by UV-visible spectrophotometry. Biological activity was evaluated in C6 glioma cells and in a proof-of-concept intracerebral C6 glioma-bearing rat model.
RESULTS: BVZ-Exo@CS-TMZ showed quasi-spherical morphology, a hydrodynamic diameter of 195.6 ± 6.7 nm, a PDI of 0.21 ± 0.03, and a zeta potential of -50.12 mV. Western blotting detected the EV-associated markers CD9, CD63, and CD81 in the Exo preparation, whereas calnexin was not detected. ELISA showed 74.9 ± 2.9% retained VEGF-binding activity after conjugation and washing. Apparent TMZ entrapment efficiency was 68.50 ± 2.15%, with a final trehalose-free loading of 15.96 ± 0.18 wt%. Apparent release over 96 h was acid-accelerated (Korsmeyer-Peppas n = 0.448-0.497). In C6 cells, the formulation reduced metabolic viability to 37.9% and lowered the TMZ-equivalent apparent IC5 0 from 99.4 to 55.6 µM. In vivo, it produced the smallest tumour area and fewest H&E-defined vascular-like regions, with increased Tp53, Bax, and Casp3 transcripts and reduced pri-/pre-miR-21 precursor RNA.
CONCLUSION: These findings support BVZ-Exo@CS-TMZ as a proof-of-concept EV-associated chitosan nanomedicine strategy for experimental glioma. Further pharmacokinetic, biodistribution, safety, and mechanistic validation in more clinically relevant glioblastoma models is required.
METHODS: CS-TMZ nanoparticles were prepared by ionotropic gelation, non-covalently associated with adipose-derived stromal cell exosomes (Exo), and functionalized with BVZ via EDC/NHS conjugation to accessible surface carboxyl groups. The Exo preparation was characterized by Western blotting, while the final formulation was characterized by FTIR, XRD, FESEM, TEM, DLS, zeta potential, and VEGF-binding ELISA. Apparent TMZ retention, loading, and release were quantified by UV-visible spectrophotometry. Biological activity was evaluated in C6 glioma cells and in a proof-of-concept intracerebral C6 glioma-bearing rat model.
RESULTS: BVZ-Exo@CS-TMZ showed quasi-spherical morphology, a hydrodynamic diameter of 195.6 ± 6.7 nm, a PDI of 0.21 ± 0.03, and a zeta potential of -50.12 mV. Western blotting detected the EV-associated markers CD9, CD63, and CD81 in the Exo preparation, whereas calnexin was not detected. ELISA showed 74.9 ± 2.9% retained VEGF-binding activity after conjugation and washing. Apparent TMZ entrapment efficiency was 68.50 ± 2.15%, with a final trehalose-free loading of 15.96 ± 0.18 wt%. Apparent release over 96 h was acid-accelerated (Korsmeyer-Peppas n = 0.448-0.497). In C6 cells, the formulation reduced metabolic viability to 37.9% and lowered the TMZ-equivalent apparent IC5 0 from 99.4 to 55.6 µM. In vivo, it produced the smallest tumour area and fewest H&E-defined vascular-like regions, with increased Tp53, Bax, and Casp3 transcripts and reduced pri-/pre-miR-21 precursor RNA.
CONCLUSION: These findings support BVZ-Exo@CS-TMZ as a proof-of-concept EV-associated chitosan nanomedicine strategy for experimental glioma. Further pharmacokinetic, biodistribution, safety, and mechanistic validation in more clinically relevant glioblastoma models is required.