ZIF-8 as a protein delivery system enhances the application of dental pulp stem cell lysate in anti-photoaging therapy

Stem cell therapy is of great therapeutical potential for anti-aging treatment. Lysates of dental pulp stem cells (DPSC) are rich in numerous cytokines, which can improve the cell growth environment and enhance collagen synthesis in the skin. Frequently, the instability of protein growth factors severely restricts their applications in living systems. In this study, a strategy for delivering the growth factors of DPSC lysate via protein-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles was developed. Using ZIF-8 as protein-encapsulated nanoparticles, a ZIF-8@DPSC lysate (ZIF-8@DL) with pH-responsive drug release was produced. ZIF-8@DL demonstrated superior cutaneous uptake, cutaneous penetration, and retention capacity in vivo compared to DPSC lysate. Moreover, ZIF-8@DL demonstrated excellent in vitro and in vivo biocompatibility. Subcutaneous microneedle injection of ZIF-8@DL into a mouse photoaging model resulted in significantly improved epidermal thickness, dermal collagen deposition, and cutaneous inflammation, with no apparent adverse effects. This study provides a safe and efficient method for enhancing the therapeutic application of DPSC lysate. It has the potential to expedite the clinical implementation of lysate-based anti-photoaging therapy.