Yang Zhipeng, Liu Yanjie, Li Haoyuan, Tang Qisheng, Yang Biao, Shi Zhifeng, Mao Ying
Institute of Biomedical Engineering and Technology, Academy for Engineering & Technology, Fudan University, Shanghai 200433, China.
Henan University of Chinese Medicine, Zhengzhou 200433 Henan, China.
Biomacromolecules. 2024 Feb 12;25(2):655-665. doi: 10.1021/acs.biomac.3c00846. Epub 2024 Jan 19.
The blood-brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases.
血脑屏障（BBB）和耐药性给胶质母细胞瘤（GBM）的化疗带来了挑战。设计了一种具有优异生物相容性和生物降解性的微针（MN）贴片，以绕过血脑屏障，并将替莫唑胺（TMZ）和PLCG1-siRNA直接释放到肿瘤部位，用于GBM的协同治疗。TMZ和PLCG1-siRNA的共递送增强了DNA损伤和细胞凋亡。这种增强背后的潜在机制是敲低PLCG1的表达，PLCG1可正向调节信号转导和转录激活因子3基因的表达，从而阻止DNA修复并增强GBM对TMZ的敏感性。MN贴片通过植入实现长期可持续药物释放，并增加病变区域的局部药物浓度，与其他药物治疗组相比，显著延长了小鼠的存活时间。MN给药为GBM和其他中枢神经系统疾病的联合治疗提供了一个平台。
