An injectable miR181a-IFI6 nanoparticles promote high-quality healing of radiation-induced skin injury

Abstract

Radiation-induced skin injury (RISI) is the primary adverse effect and dose-limiting factor for radiotherapy, and there is no effective treatment. Interferon-alpha inducible protein 6 (IFI6) is upregulated after exposure to ionizing radiation in HaCaT cells. It significantly promotes the proliferation of these cells and reduces radiation sensitivity. miR181a also reduces radiosensitivity. Therefore, we designed materials to modify IFI6 and miR181a through the erythrocyte membrane (EM) and hemoglobin (HB) to enhance local circulation and biocompatibility and play a long-term and stable role. Structure, size, morphology, and elemental compositions of miR181a@EM-HB-IFI6 were analyzed using transmission electron microscopy, X-ray diffraction patterns, Fourier transform infrared spectroscopy, UV-Vis-NIR, zeta potential, and protein electrophoresis. Cytological studies suggested that miR181a@EM-HB-IFI6 is non-toxic to HaCaT cells, promotes their migration, vascularization, inhibits apoptosis, and expresses IFI6 after irradiation. A mouse model suggested that miR181a@EM-HB-IFI6 promotes wound healing and reduces reactive oxygen species expression. miR181a@EM-HB-IFI6 accelerates RISI healing, possibly by initiating the SSBP1/HSF1 signaling pathway. In addition, miR181a@EM-HB-IFI6 can also improve the immune microenvironment. In conclusion, IFI6 and miR181a were used as RISI wound-healing materials for the first time.

Keywords

• miRNA-181a
• Erythrocyte membrane
• Hemoglobin
• Interferon-alpha inducible protein 6
• Radiation-induced skin injury