Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing

Yaling Zheng; Wei Wang; Yao Gao; Weiyi Wang; Renwu Zhang; Dejun Wu; Luodan Yu; Yu Chen

doi:10.1016/j.mtbio.2023.100621

Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing

Mater Today Bio. 2023 Mar 31:20:100621. doi: 10.1016/j.mtbio.2023.100621. eCollection 2023 Jun.

Authors

Yaling Zheng¹, Wei Wang², Yao Gao¹, Weiyi Wang¹, Renwu Zhang³, Dejun Wu³, Luodan Yu¹, Yu Chen¹

Affiliations

¹ Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.
² Shanghai Key Laboratory of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.
³ Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230601, PR China.

Abstract

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO₂ nanodots-engineered thermosensitive chitosan hydrogel (CuO₂-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO₂ nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu²⁺, the CuO₂ nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H₂O₂ under acidic tumor microenvironment. Simultaneously, the CuO₂ nanodots with a narrow bandgap (2.29 eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (¹O₂) could be boosted by the O₂ generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.

Keywords: Antibacteria; Chemodynamic therapy; Melanoma; Sonodynamic therapy; Tissue healing.