Manganese-Functionalized GelMA Hydrogels for MRI-Guided Immunotheranostics in Precision Oncology

Abstract

Precision oncology requires multifunctional platforms capable of integrating accurate tumor diagnosis, localized therapeutic delivery, immune modulation, and real-time monitoring of treatment response. Gelatin methacryloyl (GelMA) hydrogels have emerged as versatile biomaterials for biomedical engineering because of their biocompatibility, extracellular matrix-like structure, tunable mechanical properties, photocrosslinkability, and capacity to incorporate therapeutic agents, imaging probes, and functional nanomaterials. In parallel, manganese-based materials have gained increasing attention as promising alternatives to gadolinium-based magnetic resonance imaging contrast agents and as therapeutic components capable of modulating the tumor microenvironment. Manganese ions and manganese-based nanomaterials can enhance T1-weighted MRI contrast, generate reactive oxygen species, relieve tumor hypoxia, deplete glutathione, promote immunogenic cell death, and activate the cyclic GMP-AMP synthase-Stimulator of Interferon Genes pathway. The integration of manganese-based systems with GelMA hydrogels offers a promising strategy for developing localized, stimuli-responsive, and MRI-guided immunotheranostic platforms. This review summarizes the fundamental properties of GelMA hydrogels, the diagnostic and therapeutic roles of manganese-based materials, strategies for constructing manganese-functionalized GelMA systems, and their potential applications in precision oncology. Current challenges, including manganese-associated toxicity, controlled ion release, mechanical optimization, reproducibility, and clinical translation, are also discussed. Finally, future directions are proposed for the rational design of safe, scalable, and personalized manganese-functionalized GelMA platforms for cancer diagnosis and therapy.