Enhanced NO-induced angiogenesis via NO/H2S co-delivery from self-assembled nanoparticles

Abstract

Nitric oxide (NO) and hydrogen sulfide (H₂S) have been the focus of research as therapeutic agents because of their biological functions. The controlled release of NO and H₂S can enhance NO-induced angiogenesis by H₂S inhibiting PDE5A. Polymeric carriers have been researched to deliver gasotransmitters and used as therapeutic agents because of their important ability to help control the concentration of NO and H₂S. Here, NO/H₂S-releasing nanoparticles were self-assembled from carboxyl-functionalized mPEG-PLGH-thiobenzamide [(methoxy poly (ethylene glycol-b-lactic-co-glycolic-co-hydroxymethyl propionic acid)-thiobenzamide)], PTA copolymer and encapsulated diethylenetriamine NONOate (DETA NONOate). The PTA copolymers were characterized by FT-IR and ¹H NMR, and the PTA-NO nanoparticles (PTA-NO-NPs) were confirmed to have core–shell structures with a size of about 140 nm. The PTA-NO-NPs were demonstrated to be biocompatible with viabilities above 100% in various cell types, with a sustained NO and H₂S releasing behavior over 72 h. Co-releasing NO and H₂S accelerated tube formation by HUVECs compared to the only NO- or H₂S-releasing groups in vitro. Also, PTA-NO-NPs performed enhanced angiogenesis compared to the control groups with statistically significant differences ex vivo. These results indicate the feasibility of medical applications through NO and H₂S crosstalk.