Acid-responsive H2-releasing nanoparticles for cancer therapyScientific Research

Abstract:

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.