Development of organic–inorganic hybrid nanoparticles for biomedical applications

Abstract Organic–inorganic hybrid nanomaterials constructed through supramolecular assembly have emerged as versatile platforms that integrate the dynamic functionalities of biomacromolecules with the distinctive physicochemical properties of inorganic components. In this Focus Review, the design principles and biomedical applications of hybrid nanosystems based on physically crosslinked nanogels derived from self-assembling polysaccharides are highlighted, as exemplified by cholesterol-bearing pullulan. These nanogels form a hydrated nanospace that enables the encapsulation of chaperone-bearing proteins while simultaneously accommodating hydrophobically modified inorganic nanoparticles. Recent advances in three representative classes of hybrid systems are summarized. First, magnetic nanogels incorporating iron oxide nanoparticles enable magnetically guided intracellular protein delivery, facilitating efficient cytosolic transduction and exhibiting in vivo therapeutic efficacy, including tumor suppression. Second, upconversion nanoparticle–nanogel hybrids function as near-infrared light-activatable platforms for photodynamic therapy, in which precise supramolecular organization enhances efficient energy transfer to photosensitizers, thereby promoting the generation of reactive oxygen species. Third, boron-containing nanogels and hybrid systems incorporating boronic oxide nanoparticles have been developed for boron neutron capture therapy, resulting in improved tumor accumulation and enhanced therapeutic outcomes. Together, these systems illustrate how supramolecularly engineered nanogels can serve as adaptive scaffolds for integrating multiple functional modalities, thereby addressing key challenges in protein delivery, phototherapy, and radiation-based treatment strategies. The modularity, biocompatibility, and structural tunability of these hybrid nanosystems provide a unifying framework for next-generation nanomedicine, with broad potential applications in cancer therapy, regenerative medicine, and related biomedical fields.