College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China.
College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China.
Colloids Surf B Biointerfaces. 2022 Jul;215:112505. doi: 10.1016/j.colsurfb.2022.112505. Epub 2022 Apr 15.
Temozolomide (TMZ), as the first-line chemotherapeutic agent, relies on inducing DNA methylation of O-guanine for treating glioma. However, the survival time of patients are hardly exceeded 14.5 months, attributing to inevitable drug resistance and systematic toxicity after long-term administration. Herein, reassembly-exosomes (R-EXO) deriving from homologous glioma cells is proposed to carry TMZ and Dihydrotanshinone (DHT) for reversing drug resistance and enhancing lesions-targeted drug delivery, defined as R-EXO-TMZ/DHT (R-EXO-T/D). It is found that R-EXO-T/D share various advantages, including preferable blood-brain barrier (BBB)-penetrating ability with nanomemter size, tumor-homing accumulation with homologous effects, as well as potentiated antitumor activity with overcoming TMZ resistance and triggering immune response. This work develops a new strategy for site-specific drug delivery, showing a promising application of drug compatibility in glioma treatment.
替莫唑胺（TMZ）作为一线化疗药物，依赖于诱导 O-鸟嘌呤的 DNA 甲基化来治疗神经胶质瘤。然而，由于长期给药后不可避免的药物耐药性和系统毒性，患者的生存时间很难超过 14.5 个月。在此，提出了源自同源神经胶质瘤细胞的重组外泌体（R-EXO）来携带 TMZ 和二氢丹参酮（DHT），以逆转耐药性并增强病变靶向药物传递，定义为 R-EXO-TMZ/DHT（R-EXO-T/D）。研究发现，R-EXO-T/D 具有多种优势，包括具有纳米尺寸的更好的血脑屏障（BBB）穿透能力、具有同源效应的肿瘤归巢积累以及通过克服 TMZ 耐药性和触发免疫反应来增强抗肿瘤活性。这项工作为靶向药物传递开发了一种新策略，为药物兼容性在神经胶质瘤治疗中的应用提供了广阔前景。
