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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. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy through the combination of CDT and chemotherapy. Here we report a pH/ROS dual‐responsive nanomedicine consisting of β‐lapachone (Lap), a pH‐responsive polymer, and a ROS‐responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH‐triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS‐induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor‐drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy. [ABSTRACT FROM AUTHOR]

Abstract: The approach of concurrent‐to‐synchronous chemoradiation has now been advanced by well‐designed nanovesicles that permit X‐ray irradiation‐triggered instant drug release. The nanovesicles consist of Au nanoparticles tethered with irradiation labile linoleic acid hydroperoxide (LAHP) molecules and oxidation‐responsive poly(propylene sulfide)‐poly(ethylene glycol) (PPS‐PEG) polymers, where DOX were loaded in the inner core of the vesicles (Au‐LAHP‐vDOX). Upon irradiation, the in situ formation of hydroxyl radicals from LAHP molecules triggers the internal oxidation of PPS from being hydrophobic to hydrophilic, leading to degradation of the vesicles and burst release of cargo drugs. In this manner, synchronous chemoradiation showed impressive anticancer efficacy both in vitro and in a subcutaneous mouse tumor model by one‐dose injection and one‐time irradiation. [ABSTRACT FROM AUTHOR]