School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.
The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.
Adv Healthc Mater. 2015 Jun 3;4(8):1203-14. doi: 10.1002/adhm.201400751. Epub 2015 Mar 19.
A novel blended nanoparticle (NP) system for the delivery of anticancer drugs and its surprisingly high efficacy for cancer chemotherapy by blending a targeting polymer folic acid-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (FA-PEG-b-PLGA) and a miscible structurally similar polymer D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactide-co-glycolide) (TPGS-PLGA) is reported. This blended NP system can be achieved through a simple and effective nanoprecipitation technique, and possesses unique properties: i) improved long-term compatibility brought by PEG-based polymers; ii) reduced multidrug resistance mediated by P-glycoprotein (P-gp) in tumor cells and increased bioavailability of anticancer drugs by incorporation of TPGS; iii) the regulation of controlled release through polymer ratios and active targeting by FA. Both in vitro cell experiments and in vivo antitumor assays demonstrated the reported blended NP system can achieve the best therapeutic efficiency in an extremely safe, simple and highly efficient process for cancer therapy. Moreover, this NP system is highly efficient in forming NPs with multiple functions, without repeated chemical modification of polymers, which is sometimes complex, inefficient and high cost. Therefore, the development of this novel blended NP concept is extremely meaningful for the application of pharmaceutical nanotechnology in recent studies.
本文报道了一种新型的混合纳米粒子(NP)系统,用于输送抗癌药物,通过混合靶向聚合物叶酸-聚乙二醇-b-聚(乳酸-共-乙醇酸)(FA-PEG-b-PLGA)和可混溶的结构类似聚合物 D-α-生育酚聚乙二醇 1000 琥珀酸-聚(乳酸-共-乙醇酸)(TPGS-PLGA),该混合 NP 系统可以通过简单有效的纳米沉淀技术实现,并具有独特的性质:i)基于 PEG 的聚合物带来的长期相容性提高;ii)通过加入 TPGS 减少肿瘤细胞中 P-糖蛋白(P-gp)介导的多药耐药性,提高抗癌药物的生物利用度;iii)通过聚合物比例调节和 FA 的主动靶向实现控制释放。体外细胞实验和体内抗肿瘤实验均表明,所报道的混合 NP 系统可在一种极其安全、简单、高效的癌症治疗过程中实现最佳治疗效果。此外,该 NP 系统在形成具有多种功能的 NPs 方面非常高效,无需对聚合物进行多次化学修饰,而这有时是复杂、低效和高成本的。因此,这种新型混合 NP 概念的发展对于药物纳米技术在最近研究中的应用具有极其重要的意义。