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

• Published in: Biomaterials science 2021-07, Vol.9 (15), p.515-5159
• Main Authors: Lee, Jieun, Yang, Chungmo, Ahn, Sangeun, Choi, Yeonjeong, Lee, Kangwon
• Format: Article
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/d1bm00448d

Nitric oxide (NO) and hydrogen sulfide (H 2 S) have been the focus of research as therapeutic agents because of their biological functions. The controlled release of NO and H 2 S can enhance NO-induced angiogenesis by H 2 S 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 H 2 S. Here, NO/H 2 S-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 1 H 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 H 2 S releasing behavior over 72 h. Co-releasing NO and H 2 S accelerated tube formation by HUVECs compared to the only NO- or H 2 S-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 H 2 S crosstalk. The simultaneous delivery of NO and H 2 S from prepared self-assembled polymeric nanoparticles shows advantages of a controlled release concentration and improved angiogenic properties in vitro and ex vivo by a synergistic effect.