Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen-doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared-photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction. The proposed catalysis-mediated SME regulation strategy will open a window to realize facile and efficient arthritis treatment.
Hydrogen gas therapy as an emerging and promising therapy strategy has overwhelming advantages especially in bio-safety compared with other gas therapy routes, but is facing a great challenge in the long-term, highly-concentrated, deeply-seated disease site-specific administration of hydrogen gas, owing to its low solubility, high but aimless diffusibility in vivo. Herein, we propose to construct an ammonia borane-loaded mesoporous silica nanomedicine (AB@MSN) to realize the intratumoral high-payload delivery and in situ acid-controlled release of hydrogen gas. The constructed AB@MSN nanomedicine has a superhigh H2 loading capacity (130.6 mg/g, more than 1370 times higher than that of the traditional H2@liposome nanomedicine) and a highly acid-responsive sustained release behavior, exhibiting high anticancer efficacies and high bio-safety in vitro and in vivo. The proposed nanomedicine-based strategy opens a new window for precision high-efficacy hydrogen therapy.