Boosting antitumor efficacy of nanoparticles by modulating tumor mechanical microenvironment

Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the tumor mechanical microenvironment, characterized by dense extracellular matrix (ECM), high tumor stiffness and solid stress, leads to only 0.7% of administered dose accumulating in solid tumors and even fewer ( similar to 0.0014%) reaching tumor cells, limiting the therapeutic eff i cacy of nanoparticles. Furthermore, the tumor mechanical microenvironment can regulate tumor cell stemness, promote tumor invasion, metastasis and reduce treatment eff i cacy. In this review, methods detecting the mechanical are introduced. Strategies for modulating the mechanical microenvironment including elimination of dense ECM by physical, chemical and biological methods, disruption of ECM formation, depletion or inhibition of cancer-associated fi broblasts, are then summarized. Finally, prospects and challenges for further clinical applications of mechano-modulating strategies to enhance the therapeutic eff i cacy of nanomedicines are discussed. This review may provide guidance for the rational design and application of nanoparticles in clinical settings. Copyright (c) 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).