Smart responsive hydrogels combined with AI design for tumor therapy

Advances in cancer therapy have underscored the critical need for multifunctional platforms that enable precise targeting, controlled drug release, and immunomodulation. Hydrogels, as transformative tools with programmable drug release capabilities, microenvironmental responsiveness, and immunoregulatory properties, demonstrate broad application prospects. This review focuses on the design and application of functionalized hydrogels, emphasizing their responsiveness to multiple stimuli, including temperature, pH, reactive oxygen species (ROS), and enzymes. It provides an in-depth analysis of their multimodal synergistic therapeutic mechanisms, including photothermal therapy, immunotherapy, starvation therapy, intelligent detection, targeted capture, and tumor microenvironment (TME) simulation. Meanwhile, recent developments in machine learning-enabled intelligent hydrogel technologies have driven the transformation of materials into intelligent systems with "smart design-perception-decision" capabilities. Although the literature on smart hydrogels has made significant progress in exploring mechanisms and optimizing performance, systematic reviews of artificial intelligence (AI)-driven platforms remain notably lacking. This paper systematically summarizes the regulatory strategies of material-derived intelligent hydrogels, AI-enabled mechanisms, and practical application cases, revealing core challenges and future development directions, thereby providing theoretical guidance and practical pathways for next-generation hydrogels in personalized and multimodal cancer therapy.