Intratumoral high-payload delivery and acid-responsive release of H 2 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.

Acid-responsive H2-releasing Fe nanoparticles for safe and effective cancer therapy

Hydrogen therapy is an emerging and promising strategy for treatment of inflammation-related diseases owing to excellent bio-safety of hydrogen molecule (H2), but is facing a challenge that the H2 concentration at the local disease site is hardly accumulated because of its high diffusibility and low solubility, limiting the efficacy of hydrogen therapy. Herein, we propose a nanomedicine strategy of imaging-guided tumor-targeted delivery and tumor microenvironment-triggered release of H2 to address the issue, and develop a kind of biocompatible carboxymethy cellulose (CMC)-coated/stabilized Fe (Fe@CMC) nanoparticles with photoacoustic imaging (PAI), tumor targeting and acid responsive hydrogen release properties for cancer therapy. The Fe@CMC nanoparticles have demonstrated high intratumoral accumulation capability, high acid responsiveness, excellent PAI performance, selective cancer-killing effect and high bio-safety in vitro and in vivo. Effective inhibition of tumor growth is achieved by intravenous injection of the Fe@CMC nanoparticles, and the selective anti-cancer mechanism of Fe@CMC is discovered to be originated from the energy metabolism homeostasis regulatory function of released H2. The proposed nanomedicine-mediated hydrogen therapy strategy will open a new window for precision, high-efficacy and safe cancer treatment.