Phospholipid‐Like Prodrug Liposomes with High Drug‐carrier Affinity and High Tumor Selectivity: Strong Competitors of Paclitaxel Nanomedicines

作者：Danping Wang, Shanhui Xu, Si Zheng, Rong Chai, Zhiyu Kuang, Yixin Sun, Yaqi Li, Shiyi Zuo, Xiang Gao, Xin Li, Qikun Jiang, Zhonggui He, Jin Sun, Hongrui Lei, An‐Hua Wang, Bingjun Sun · 发表于：Advanced Functional Materials · 年份：2025 · DOI：10.1002/adfm.202502341 · 被引用次数：4 · 研究领域：RNA Interference and Gene Delivery、Nanoparticle-Based Drug Delivery、Advanced biosensing and bioanalysis techniques

Abstract Paclitaxel (PTX) is an effective agent against a wide spectrum of solid tumors. Lipusu is the first and only marketed liposomal PTX product in the world. However, it is hindered by the insufficient affinity between PTX and phospholipids, resulted in a low drug loading (≈5.68%), poor stability, and limited antitumor efficacy. Inspired by the structural characteristics of phospholipids, a phospholipid‐like PTX prodrug (PTX‐OCT) is designed to construct prodrug liposomes (PTX‐OCT PLs). Compared with Lipusu, PTX‐OCT PLs possessed a smaller particle size (135 vs 400 nm) with a higher drug loading (10.52% vs 5.68%, equal to PTX). Meanwhile, PTX‐OCT PLs would deliver PTX efficiently in vivo evidenced by the AUC higher than Lipusu (≈170‐fold) due to their superior stability. The introduction of disulfide bonds endowed PTX‐OCT PLs with the capacity of intelligent activation, which is the key element for tumor selectivity. With such characterizations, PTX‐OCT PLs exhibited potent antitumor efficacy with good tolerance in 4T1‐bearing model, even better than Abraxane and Lipusu. To summarize, this work designed PTX nanomedicines with potential market competitiveness and enriched the theoretical basis of designing advanced nanomedicines for efficient cancer treatment.