Intratumoral high-payload delivery and acid-responsive release of H₂ for efficient cancer therapy using the ammonia borane-loaded mesoporous silica nanomedicine

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.