BSA-ICG-Cu(<scp>ii</scp>) complex as an NIR-responsive multifunctional platform for wound healing: deciphering therapeutic action <i>in vitro</i>

Therapeutic platforms suitable for NIR-responsive antimicrobial treatments through photothermal and photodynamic modalities are gaining attention in treating chronic wounds. The efficiency of such platforms can be further enhanced by making them angiogenic and a promoter of fibroblast activities. Herein, we report a novel molecular platform composed of bovine serum albumin (BSA), indocyanine green (ICG) and bivalent copper (Cu(ii)) using green chemistry by exploiting the affinity of ICG and Cu(ii) ions towards BSA. We hypothesized that in the BSA-ICG-Cu(ii) complex, ICG will help in producing heat and reactive oxygen species under NIR (808 nm) exposure, which can kill bacteria; Cu(ii) will induce angiogenesis and BSA will activate dermal fibroblasts. The SEM images of the BSA-ICG-Cu(ii) complex revealed a bead and fibril structure at the microscale. Biophysical studies (UV-vis-NIR, fluorescence and CD spectroscopy) indicated stable complex formation through the involvement of the hydrophobic BSA core. A study on NIR-mediated (808 nm LASER) killing of bacteria (<i>S. aureus</i> and <i>E. coli</i>) confirmed the photothermal and photodynamic efficiencies of the BSA-ICG-Cu(ii) complex. At the cellular level, dermal fibroblasts, when treated with the BSA-ICG-Cu(ii) complex, showed significant enhancement in cell migration and cellular VEGF expression (∼2.8 fold). The <i>in vitro</i> angiogenesis study using HUVEC cells demonstrated that the complex can promote tube formation. In conclusion, the BSA-ICG-Cu(ii) complex can serve as a multifunctional NIR-responsive therapeutic platform capable of exerting antibacterial, angiogenic and fibroblast-activating properties, which are beneficial for chronic wound therapy.