State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China; Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
Biomaterials. 2015 Jul;56:229-40. doi: 10.1016/j.biomaterials.2015.03.050. Epub 2015 Apr 21.
Nanoparticles (NPs) have great potential as drug delivery systems or as drugs for treating certain diseases. We designed three NPs with different charges and modifications with PEG to treat tumors. PDLA-CS, PEG-PLGA-PLL, and PEG-PS/CaP NPs were designed and evaluated to assess NPs fate in vivo and efficacy for treating tumors. Comparison between PEG-modified and non-PEG-modified NPs showed that PEG-modified NPs increased K(+) efflux, easily escaped from lysosomes, affected the mitochondria, induced mitochondrial apoptosis, had longer circulation time, and easily targeted tumors. Non-PEG-modified NPs induce the endoplasmic reticulum apoptosis pathway. Comparison between positively and negatively charged NPs showed that negatively charged NPs have less effect on the K(+) efflux of normal cells and more effect on the mitochondrial apoptosis of tumor cells. Positively charged NPs accumulated within the tumors and the liver and lungs. These results provide a theoretical basis for future clinical applications.
纳米粒子（NPs）作为药物传递系统或治疗某些疾病的药物具有巨大的潜力。我们设计了三种带有不同电荷和聚乙二醇（PEG）修饰的 NPs 来治疗肿瘤。设计并评估了 PDLA-CS、PEG-PLGA-PLL 和 PEG-PS/CaP NPs，以评估 NPs 在体内的命运和治疗肿瘤的疗效。PEG 修饰和非 PEG 修饰 NPs 的比较表明，PEG 修饰的 NPs 增加了 K(+)外排，容易从溶酶体逃逸，影响线粒体，诱导线粒体凋亡，具有更长的循环时间，并且容易靶向肿瘤。而非 PEG 修饰的 NPs 则诱导内质网凋亡途径。正电荷和负电荷 NPs 的比较表明，负电荷 NPs 对正常细胞 K(+)外排的影响较小，对肿瘤细胞线粒体凋亡的影响较大。正电荷 NPs 在肿瘤、肝脏和肺部积累。这些结果为未来的临床应用提供了理论依据。
