The high affinity of positively charged nanoparticles to biological interfaces makes them easily taken up by tumor cells but limits their tumor permeation due to non-specific electrostatic interactions. In this study, polyion complex coated nanoparticles with different charge reversal profiles were developed to study the influence of charge reversal profile on tumor penetration. The system was constructed by polyion complex coating using micelles composed of poly (lysine)-b-polycaprolactone (PLys-b-PCL) as the cationic core and poly (glutamic acid)-g- methoxyl poly (ethylene glycol) (PGlu-g-mPEG) as the anionic coating material. Manipulation of charge reversal profile was achieved by controlling the polymer chain entanglement and electrostatic interaction in the polyion complex layer through glutaraldehyde-induced shell-crosslinking. The delayed charge reversal nanoparticles (CTCL30) could maintain negatively charged in pH 6.5 PBS for at least 2h and exhibit pH-responsive cytotoxicity and cellular uptake in an extended time scale. Compared with a faster charge reversal counterpart (CTCL70) with similar pharmacokinetic profile, CTCL30 showed deeper penetration, higher in vivo tumor cell uptake and stronger antitumor activity in vivo (tumor inhibition rate: 72.3

作者：Jingxin, Gou；Yuheng, Liang；Linlin, Miao；Wei, Guo；Yanhui, Chao；Haibing, He；Yu, Zhang；Jingyu, Yang；Chunfu, Wu；Tian, Yin；Yanjiao, Wang；Xing, Tang

来源：Acta biomaterialia 2017 年