Exquisite Vesicular Nanomedicine by Paclitaxel Mediated Co‐assembly with Camptothecin Prodrug

Abstract We report that the self‐assembly of drug amphiphiles, Evans blue conjugated camptothecin prodrug (EB‐CPT), can be modulated by another anticancer drug paclitaxel (PTX), resulting in ultrahigh quality of nanovesicles (NVs) with uniform shape and diameters of around 80 nm with the EB‐CPT:PTX weight ratio of 1:1, 1:2, and 1:3, denoted as ECX NVs. Significantly, the co‐assembly of EB‐CPT and PTX without adding other excipients has nearly 100 % drug loading efficiency (DLE) and ultrahigh drug loading content (DLC) of PTX alone of up to 72.3±1.7 wt % which, to our best knowledge, is among the highest level reported in literature. Moreover, the ECX NVs with the EB‐CPT:PTX weight ratio of 1:2 showed remarkable combination index of 0.59 at a level of 50 % efficacy against HCT116 cells in vitro and greatly improved tumor inhibition effect in vivo compared with two clinically approved CPT‐ and PTX‐based anticancer nanomedicines (Onivyde and Abraxane) individually and their combinations.