Amphiphilic hemin-based nanoparticles with hypoxia tolerance and inflammation inhibition for osteoarthritis therapy.

Osteoarthritis (OA) remains a major clinical challenge, driven by persistent cytokine-based inflammation and poor regenerative capacity of hypoxic microenvironment and avascular cartilage. Despite recent advances, strategies that concurrently address inflammation and tissue repair remain elusive. Here, we report a dual-functional, injectable nanoparticle system based on amphiphilic hemin, a naturally derived hemoglobin prosthetic group, for the synergistic treatment of OA. Harnessing its amphiphilic properties, hemin self-assembles into nanocarriers capable of encapsulating hydrophobic anti-inflammatory agents, enhancing their solubility, bioavailability, and sustained release within the joint microenvironment. Beyond serving as a carrier, hemin itself activates hemoglobin-associated pathways to support chondrocyte survival and function under inflammatory and hypoxic stress. This work uncovers an unexpected therapeutic role - hypoxia tolerance for hemin in OA and establishes a versatile platform for hydrophobic drug delivery in inflammatory settings, with broader implications for the treatment of chronic inflammatory and degenerative diseases.