Advances of curcumin-loaded hydrogels for multimodal cancer therapeutics

Abstract Curcumin, a natural polyphenol with multifaceted anticancer properties, faces significant clinical translation challenges due to poor solubility, rapid metabolism, and low bioavailability. Hydrogels, as biocompatible and tunable drug delivery platforms, have emerged as a transformative strategy to overcome these limitations. This review highlights recent advancements in curcumin-hydrogel systems, emphasizing stimuli-responsive designs (e.g., pH-, temperature-, and light-activated mechanisms), combinatorial therapies, and applications across diverse cancer models. Innovations such as miRNA co-delivery, metallo-pharmaceutical hybrids, and dual-functional hydrogels with antimicrobial activity are explored, demonstrating enhanced spatiotemporal control, targeted delivery, and synergistic therapeutic outcomes. Combinatorial approaches integrating curcumin with chemotherapeutics, photothermal agents, or epigenetic modulators amplify anticancer efficacy by simultaneously disrupting oncogenic pathways and reversing chemoresistance. Compared with existing reviews, this work provides a comprehensive synthesis of emerging intelligent hydrogel technologies-including AI-integrated predictive release systems, multi-stimuli-responsive platforms, and CRISPR-immunotherapy hybrids-specifically within the context of cancer therapy, thereby systematically linking advanced material design with multimodal treatment strategies. Despite these advancements, challenges such as pH-dependent degradation, formulation stability, and clinical scalability persist. The review also emphasizes the paradigm-shifting potential of systems enabling precision targeting of chemoresistant tumors while modulating immune checkpoints.