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. In this work, hydrophobicity-adaptive polymers based on poly(N-isopropylacrylamide) are anchored to tumor-cell-derived MPs for enhanced delivery of the anticancer drug doxorubicin (DOX). The polymers are hydrophilic in blood to prolong the circulation time of DOX-loaded MPs (DOX@MPs), while rapidly switching 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. The work provides a facile and simple strategy for improved anticancer drug delivery of tumor-cell-derived MPs. Hydrophobicity-adaptive polymers based on poly(N-isopropylacrylamide) are anchored to tumor-cell-derived microparticles (MPs) for enhanced delivery of anticancer drug doxorubicin (DOX). The hydrophobicity of polymers at the tumor acidic microenvironment drives the fission of MPs to form small vesicles, facilitating tumor accumulation, deep tumor penetration, and efficient internalization of DOX@MPs into tumor cells and cancer stem cells.image

Automated summary

This study presents a simple and effective strategy for improving the delivery of anticancer drugs using hydrophobicity-adaptive polymers anchored to tumor-cell-derived microparticles (MPs). These polymers switch to hydrophobicity in the tumor acidic microenvironment, promoting the fission of MPs into small vesicles, facilitating drug accumulation, deep penetration into tumors, and efficient intracellular uptake.