Tumor Microenvironment‐Responsive Polymer Delivery Platforms for Cancer Therapy

Y Yiqi Shi (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 P.R. China) Q Qianqian Yu L Lijie Tan Q Qi Wang W Wei‐Hong Zhu (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center For Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China)

Abstract

Abstract Most chemotherapeutic and bioimaging agents struggle with inadequate bioavailability, primarily due to their limited biocompatibility and lack of specificity in targeting, leading to low or decreased anticancer efficacy and inaccurate imaging. To surmount these obstacles, the development of stimuli‐responsive polymer delivery platforms, predominantly leveraging the tumor microenvironment (TME), has emerged as a promising strategy. Therapeutic and diagnostic agents can be released controllably at the tumor site by virtue of the bond cleavage or hydrophobic to hydrophilic transformation of TME‐sensitive linkages in TME‐responsive systems, thus augmenting cancer treatment and imaging precision, while simultaneously attenuating the damage to healthy tissues and false imaging signals caused by non‐specific drug leakage. In this comprehensive review, we scrutinize recent studies of TME‐responsive polymer delivery platforms, encompassing pH‐, ROS‐, GSH‐, enzyme‐, and hypoxia‐responsive vectors, significantly from the perspective of their molecular design and responsive mechanism, and further summarizing their bio‐application in drug delivery and diagnostic imaging. Moreover, this review encapsulates the critical challenges and offers an insightful perspective on the future prospects of TME‐responsive polymer delivery platforms in terms of molecular and vector design.

Article Details

Volume / Issue Vol. 64, Issue 26
Published June 24, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (5)

Y

Yiqi Shi

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 P.R. China

Q

Qianqian Yu

L

Lijie Tan

Q

Qi Wang

W

Wei‐Hong Zhu

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center For Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China