Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy^†

Abstract

Comprehensive SummaryTumor stroma composing diverse extracellular matrixes (ECM) and stromal cells shapes a condensed physical barrier, which severely hampers the efficient accessibility of nanomedicine to tumor cells, especially these deep‐seated in the core of tumor. Such barrier significantly compromises the antitumor effects of drug‐loaded nanomedicine, revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration ability. To achieve this goal, various nanoparticle‐based strategies have been developed, including direct depleting ECM components via delivering anti‐fibrotic agents or targeting stromal cells to suppress ECM expression, dynamic regulation of nanoparticles’ physicochemical properties (i.e., size, surface charge, and morphology), mechanical force‐driven deep penetration, and natural/biomimetic self‐driven nanomedicine. All these nanostrategies were systemically summarized in this review, and the design principles for obtaining admirable nanomedicine were included. With the rapid development of nanotechnology, elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies, such as chemotherapy, photodynamic therapy, and immunotherapy.This article is protected by copyright. All rights reserved.