Polymeric Nanoparticles Simultaneously Delivering Paclitaxel Prodrug and Combretastatin A4 with Exceptionally High Drug Loading for Cancer Combination Therapy
Huicong Zhou, Zhaofan Yang, Guan-Yu Jin, Lanqing Wang, Yuanzhen Su, Hao Liu, Hai Sun, Ling‐Wei Xue, Liwei Mi, Irina A. Veselova, Mingqiang Li, Shixian Lv, Xuesi Chen
Abstract
Nanomedicines capable of delivering multiple drugs have become essential in combination therapy. However, the challenges of low drug loading capacity (DLC) and difficulties in administering dosages between different drugs significantly limit the antitumor efficacy. In this study, a nanomedicine constructed through a rational prodrug and nanocarrier design was reported for cancer combination therapy. Initially, a phenylborate ester (PBE) group-modified paclitaxel (PTX) prodrug (PTX–PBE) was synthesized and could self-assemble in water. Subsequently, combretastatin A4 (CA4) polymer conjugates, mPEG–PCA4 (PCA4), were synthesized as nanocarriers to facilitate the exceptionally high drug loading of PTX–PBE in a precisely controlled manner. Both the in vitro and in vivo experiments demonstrated that the PCA4 loading PTX–PBE nanoparticles (PCA4/PTX–PBE NPs) exhibited potent antitumor efficacy and favorable biocompatibility. Our approach provides a straightforward, efficient, and controllable strategy for the co-delivery of pharmaceuticals in clinical cancer combination therapy.