Pd Icosahedral Nanoparticles Promote Skin Wound Healing by Enhancing SP1-HBEGF Axis-Mediated Keratinocytes Proliferation

Fanping He,1– 3,* Mengfan Li,4,* Han Zhao,1,3 He Zhao,1,3 Xin Meng,1,3 Yiya Zhang,1,3,5 Yan Tang,1,3,5 Hongwen Huang,4,6 Ji Li,1,3,5 Hongfu Xie,1,3 Ben Wang1,3,5 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Plastic and Reconstructive Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4College of Materials Science and Engineering, Hunan University, Changsha, Hunan, 410082, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 6Shenzhen Research Institute of Hunan University, Shenzhen, Guangdong, 518055, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ben Wang, Email [email protected] Hongfu Xie, Email [email protected]: Impaired wound healing leads to compromised cutaneous barrier and dysfunction, which still remains a challenging problem. However, safe and efficient materials and treatments for promoting wound healing are still lacking. Metal nanoparticles especially palladium nanoparticles (Pd NPs) have attracted tremendous interests in medical application in recent years, due to its unique physicochemical properties and biological inertness. Thereinto, Pd icosahedra nanoparticles (Pd Icos NPs) and Pd octahedra nanoparticles (Pd Oct NPs) have superior catalytic activity compared to other shapes but the application in skin wound healing have not been studied and reported.Methods: Pd Oct NPs and Pd Icos NPs were synthesized by seed-mediated growth method and one-step synthesis method and characterized by series physical chemical assays. The acute full-thickness skin excision wound mouse model was used to access the wound healing potential and screen out the effective materials—Pd Icos NPs. Next evaluate the biotoxicity and safety of Pd Icos NPs and both in HaCaT cells and in vivo. Further examine related molecules expression by RT-qPCR and WB in HaCaT cells and wound tissues with Pd Icos treatment. Then knockout the related molecules both in HaCaT cells and in vivo to validate the molecular mechanism of these molecules in the phenotype of wound healing promoted by Pd Icos NPs.Results: Pd Icos NPs with surface and tensile strain rather than Pd Oct NPs can promote skin wound healing. Pd Icos NPs upregulates the expression of HBEGF by promoting the production of transcription factor SP1, and contributes to keratinocytes proliferation and accelerating acute full-thickness skin wound healing.Discussion: Pd Icos NPs represent an effective and safe material for skin wound healing, suggesting a potential novel therapeutic strategy.Keywords: palladium icosahedral nanoparticles, keratinocytes, cell proliferation, skin wound healing, HBEGF, transcription factor SP1