Tang Chunming, Wang Yanling, Wu Min, Wang Zhiji, Zhou Yupeng, Lin Ya, Wang Yijun, Xu Huae
Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Department of Pharmacy, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, China.
J Biomed Res. 2024 May 30;39(1):87-102. doi: 10.7555/JBR.38.20240100.
Glioblastoma multiforme (GBM) is a highly aggressive and lethal brain tumor with limited treatment options. To improve therapeutic efficacy, we developed a novel multifunctional nanoplatform, GM@P(T/S), comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide (TMZ) and superparamagnetic iron oxide (SPIO) nanoparticles. The successful preparation was confirmed in terms of particle size, morphology, stability, the drug release, and cellular uptake assays. We demonstrated that GM@P(T/S) exhibited the enhanced homotypic targeting, the prolonged blood circulation, and efficient blood-brain barrier penetration in both and studies. The combination of TMZ and SPIO nanoparticles within GM@P(T/S) synergistically improved chemo-radiation therapy, leading to a reduced tumor growth, an increased survival, and minimal systemic toxicity in the orthotopic GBM mouse models. Our findings suggest that GM@P(T/S) holds a great promise as a targeted and efficient therapeutic strategy for GBM.
多形性胶质母细胞瘤(GBM)是一种极具侵袭性和致命性的脑肿瘤,治疗选择有限。为提高治疗效果,我们开发了一种新型多功能纳米平台GM@P(T/S),它由包裹着GBM细胞膜的聚合物纳米颗粒组成,并同时负载了替莫唑胺(TMZ)和超顺磁性氧化铁(SPIO)纳米颗粒。通过粒径、形态、稳定性、药物释放和细胞摄取实验证实了其成功制备。我们证明,在体内和体外研究中,GM@P(T/S)均表现出增强的同源靶向性、延长的血液循环时间和高效的血脑屏障穿透能力。GM@P(T/S)中TMZ和SPIO纳米颗粒的组合协同改善了放化疗效果,导致原位GBM小鼠模型中的肿瘤生长减缓、生存期延长且全身毒性最小。我们的研究结果表明,GM@P(T/S)作为一种针对GBM的靶向高效治疗策略具有巨大潜力。