Key Laboratory of Functional Polymer Materials, Ministry of Education, and Institute of Polymer Chemistry, Nankai University, Tianjin, China.
Biomacromolecules. 2013 Feb 11;14(2):460-7. doi: 10.1021/bm301694t. Epub 2013 Jan 8.
The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i.v.). Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen. In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys) and poly(N-isopropylacrylamide)-block-poly(aspartic acid) (PNIPAM-b-PAsp) in aqueous medium. The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the (125)I-labeled MSMs determined by Gamma counter. Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i.v.. The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.
用于癌症治疗的纳米载体靶向性能不佳，主要是由于其在血液循环中迅速清除，以及主要在网状内皮系统（RES）的器官中积累，导致静脉注射（i.v.）后低效的增强渗透性和保留（EPR）效应。在此，我们报告了一种有效延长纳米颗粒血液循环并减少其在肝脏和脾脏中沉积的方法。在这项工作中，我们通过在水溶液中自组装嵌段共聚物聚乙二醇-聚赖氨酸（PEG-b-PLys）和聚（N-异丙基丙烯酰胺）-聚（天冬氨酸）（PNIPAM-b-PAsp），制备了一系列具有相近粒径、荷电和核组成但壳层中亲水/亲油比不同的混合壳层胶束（MSMs）。通过γ计数器测定（125）I 标记的 MSMs 的体内追踪，系统研究了表面不均一性对体内分布的影响。与单 PEG 化胶束相比，一些 MSMs 被证明具有显著的高效性，在静脉注射后 1 小时，肝脏和脾脏中的积累降低了 3 倍以上，血液中的浓度提高了约 6 倍。这些结果为未来开发用于有效癌症治疗的长循环纳米载体提供了一种新策略。
