Xu Cong-Fei, Zhang Hou-Bing, Sun Chun-Yang, Liu Yang, Shen Song, Yang Xian-Zhu, Zhu Yan-Hua, Wang Jun
Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei Anhui 230027, PR China.
CAS Center for Excellence in Nanoscience, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei Anhui 230027, PR China.
Biomaterials. 2016 May;88:48-59. doi: 10.1016/j.biomaterials.2016.02.031. Epub 2016 Feb 23.
The design of ideal nanoparticle delivery systems should be capable of meeting the requirements of several stages of drug delivery, including prolonged circulation, enhanced accumulation and penetration in the tumor, facilitated cellular internalization and rapid release of the active drug in the tumor cells. However, among the current design strategies, meeting the requirements of one stage often conflicts with the other. Herein, a tumor pH-labile linkage-bridged block copolymer of poly(ethylene glycol) with poly(lacide-co-glycolide) (PEG-Dlinkm-PLGA) was used for siRNA delivery to fulfill all aforementioned requirements of these delivery stages. The obtained siRNA-encapsulating PEG-Dlinkm-PLGA nanoparticle gained efficiently prolonged circulation in the blood and preferential accumulation in tumor sites via the PEGylation. Furthermore, the PEG surface layer was detached in response to the tumor acidic microenvironment to facilitate cellular uptake, and the siRNA was rapidly released within tumor cells due to the hydrophobic PLGA layer. Hence, PEG-Dlinkm-PLGA nanoparticles met the requirements of several stages of drug delivery, and resulted in the enhanced therapeutic effect of the nanoparticular delivery systems.
理想的纳米颗粒递送系统的设计应能够满足药物递送几个阶段的要求，包括延长循环时间、增强在肿瘤中的蓄积和渗透、促进细胞内化以及使活性药物在肿瘤细胞中快速释放。然而，在当前的设计策略中，满足一个阶段的要求往往与其他阶段相冲突。在此，一种由聚乙二醇与聚（丙交酯-乙交酯）通过肿瘤pH敏感连接桥接的嵌段共聚物（PEG-Dlinkm-PLGA）被用于递送siRNA，以满足上述递送阶段的所有要求。所制备的包裹siRNA的PEG-Dlinkm-PLGA纳米颗粒通过聚乙二醇化有效地延长了在血液中的循环时间，并在肿瘤部位实现了优先蓄积。此外，PEG表面层会响应肿瘤酸性微环境而脱落，以促进细胞摄取；由于疏水性的PLGA层，siRNA在肿瘤细胞内迅速释放。因此，PEG-Dlinkm-PLGA纳米颗粒满足了药物递送几个阶段的要求，并增强了纳米颗粒递送系统的治疗效果。
