Reactive oxygen species-responsive polydopamine-PtCuTe nanoparticle-loaded microneedle system for promoting the healing of infected skin wounds

• Published in: Journal of controlled release 2024-12, Vol.376, p.999-1013
• Main Authors: Che, Hongfan, Xu, Junzhi, Wu, Dong, Chen, Siliang, Liu, Chengkang, Zhao, Chongbao, Peng, Kun
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Antioxidants - administration & dosage; Antioxidants - pharmacology; biocompatibility; epithelium; Escherichia coli; Escherichia coli - drug effects; fibroblasts; granulation tissue; histology; Human Umbilical Vein Endothelial Cells; Humans; immune response; Indoles - administration & dosage; Indoles - chemistry; macrophages; Male; Mice; Microneedle; Nanoparticles; Nanoparticles - chemistry; Needles; oxygen; Polymers - chemistry; reactive oxygen species; Reactive Oxygen Species - metabolism; Scavenge reactive oxygen species; Skin - drug effects; Skin - metabolism; Staphylococcus aureus - drug effects; Tissue regeneration; viability; Wound Healing - drug effects; Wound Infection - drug therapy
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2024.11.002

Nanozymes, known for their high efficiency in scavenging reactive oxygen species (ROS), have received significant attention in promoting the healing of infected wounds. Herein, we reported a novel multifunctional PDA-PtCuTe nanozyme with excellent ROS scavenging, antibacterial, pro-angiogenic, anti-inflammatory, and immune regulatory properties. It was loaded onto microneedles (PTPP-MN) for treating infected wounds. In vitro experiments demonstrated its ability to scavenge ROS and exhibit antioxidant properties. Compared to PT-MN (11.03 ± 3.37 %) and PTP-MN (42.30 ± 2.60 %), the ROS scavenging rate of PTPP-MN reached 63.63 ± 4.42 %. The microneedle exhibits good biocompatibility, stimulating fibroblast migration, endothelial angiogenesis, and M2 macrophage polarization. Additionally, it effectively eliminates ROS and provides antioxidant effects while inhibiting the viability of S. aureus and E. coli. Animal experiments showed that the PTPP-MN group achieved near-complete re-epithelialization by the third day compared to other groups. Histological observations revealed that the PTPP-MN group exhibited enhanced granulation tissue formation, epithelial regeneration, and angiogenesis. After PTPP-MN treatment, the local immune response shifted from a pro-inflammatory state to a pro-regenerative state. Our results indicate that PTPP-MN holds great promise for infected wound healing with reduced scar formation. We have developed a type of microneedle (PTPP-MN) loaded with Polydopamine-PtCuTe antibacterial nanoparticles for the treatment of infected wound healing. The Polydopamine-PtCuTe nanozyme exhibits various capabilities in vivo, including antibacterial activity, promotion of angiogenesis, scavenging of reactive oxygen species (ROS), and M2 macrophage polarization. Microneedles were employed to achieve targeted delivery. Animal experiments demonstrated that compared to other groups, the PTPP-MN microneedle group exhibited enhanced granulation tissue formation, epithelial regeneration, and angiogenesis. After PTPP-MN treatment, the local immune response shifted from a pro-inflammatory state to a pro-regenerative state. The PTPP-MN designed in this study not only creates an optimal environment for accelerating wound healing but is also convenient for carrying, thereby providing an ideal material system for infected wounds. [Display omitted]