Hydrophobicity-Adaptive Polymers Trigger Fission of Tumor Cell-Derived Microparticles for Enhanced Anticancer Drug Delivery.

Tumor cell-derived microparticles (MPs) can function as anticancer drug delivery carriers. However, short blood circulation time, large size-induced insufficient tumor accumulation and penetration into tumor parenchyma as well as limited cellular internalization by tumor cells and cancer stem cells (CSCs), and difficult intracellular drug release restrict the anticancer activity of tumor cell-derived MP-based drug delivery systems. Here, hydrophobicity-adaptive polymers based on poly(N-isopropylacrilamide) are anchored to tumor cell-derived MPs for enhanced delivery of anticancer drug doxorubicin (DOX). The polymers are hydrophilic in blood to prolong the circulation time of DOX-loaded MPs (DOX@MPs), while rapidly switch to hydrophobic at the tumor acidic microenvironment. The hydrophobicity of polymers drives the fission of tumor cell-derived MPs to form small vesicles, facilitating tumor accumulation, deep tumor penetration and efficient internalization of DOX@MPs into tumor cells and CSCs. Subsequently, the hydrophobicity of polymers in acidic lysosomes further promotes DOX release to nuclei for strong cytotoxicity against tumor cells and CSCs. Our work provides a facile and simple strategy for improved anticancer drug delivery of tumor cell-derived MPs. This article is protected by copyright. All rights reserved.