Ascorbate/methionine-based CH delivery nanomedicine for tumor-targeted therapy.

Methane (CH) is identified to be an emerging anti-inflammation and anti-cancer molecule with high bio-safety, but the targeted delivery of CH is a thorny challenge. Herein, we propose a CH delivery strategy based on an intratumoral HO-triggered cascade reaction of ascorbic acid (AA)/methionine (Met), and have constructed a new nanomedicine (AMN) for tumor-targeted CH therapy. Encouragingly, AMN realizes the effective tumor-targeted delivery and intratumoral HO-responsive release of CH, and exhibits significant anti-cancer effects and high bio-safety. Mechanistically, we have discovered that intratumoral released CH can not only induce the apoptosis of 4T1 tumor cells by inhibiting their mitochondrial metabolism, but also activate tumor immunotherapy by reprogramming tumor-associated macrophages (TAMs) phenotype (M2 to M1). The combination of the above anti-cancer pathways by virtue of tumor-targeted CH delivery makes contribution to outstanding anti-cancer efficacy of AMN. The proposed CH delivery strategy opens a new window for safe and effective tumor therapy.