Tumor Microenvironment-Responsive Polymer Delivery Platforms for Cancer Therapy

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.