Self-assembled amino acid-based copolymer nanoparticles for wound healing and tissue regeneration: structure studied...

Amino acid-based block copolymer nanoparticles with cross-linkers have garnered growing interest in recent years. However, its intricate synthesis and purification difficulties, along with stability concerns linked to intermicellar crosslinking, restrict their potential use in healthcare and therapeutic applications. Thus, the present work aimed to design amphiphilic block copolymer nanoparticles of N-acryloyl glycine and N-acryloyl-(L-phenylalanine methyl ester), i.e., p(NAG-co-NAPA)_wc, without the use of a crosslinker via miniemulsion free radical polymerization. The self-assembled π-π stacking structural arrangement of the copolymer at different temperatures has been confirmed through molecular dynamics (MD) simulations, which corroborated the structural stability of the copolymer nanoparticles at physiological temperature (37 °C). The cell migration results of the p(NAG-co-NAPA)_wc nanoparticles are complementary to those of the CEMA assay, revealing their tissue regeneration properties. Furthermore, the in vivo wound healing study demonstrated that within 13 days post-treatment, ∼97% of the wound can be healed, whereas for the control, it was found to be only ∼80%. Additionally, the RT-PCR results revealed that the p(NAG-co-NAPA)_wc nanoparticles possess anti-inflammatory and tissue regeneration properties by downregulating TNF-α and IL-1β and upregulating PECAM-1 and VEGF-A, respectively. In conclusion, these p(NAG-co-NAPA)_wc nanoparticles are paramount with an extensive clinical potential for the regeneration of acute wounds and can be used for other therapeutic applications.