Mechanism and Progress of Stimulus-Responsive Nanoparticles in Targeted Cancer Therapy

Cancer, a disease characterized by uncontrolled cell proliferation, poses significant challenges to traditional treatments. Surgery, chemotherapy, radiotherapy, and immunotherapy, while commonly used, are limited by issues such as difficulty in eliminating micro-metastasis, poor specificity with severe side effects, radiation damage to healthy tissues, and low patient response rates. Stimulus-responsive nanoparticles have emerged as a promising precision drug delivery strategy to address these limitations. They achieve targeted drug accumulation and controlled release by leveraging unique features of the tumor microenvironment (e.g., acidic pH, overexpressed enzymes like MMPs, and elevated ROS levels) and exogenous stimuli (e.g., light). Key types include pH-responsive nanoparticles, which rely on pH differences between tumor and normal tissues; enzyme-responsive nanoparticles, activated by specific overexpressed enzymes in tumors; and ROS-responsive nanoparticles, triggered by high ROS concentrations in the tumor microenvironment, each with distinct mechanisms and applications. However, their clinical translation faces challenges such as tumor microenvironment heterogeneity, biocompatibility concerns, insufficient drug release control, and limited tumor penetration. Future prospects lie in multi-stimulus synergistic therapy, intelligent and personalized design, combination with other therapeutic approaches, and the development of novel materials. This article reviews the mechanism, progress, challenges, and future directions of stimulus-responsive nanoparticles in targeted cancer therapy.