Beyond antibiotics: 3d-transition metal ions − serum albumin −indocyanine green complex as a novel multifunctional NIR-responsive therapeutic platform for treating diabetic foot ulcer

Abstract

Diabetic Foot Ulcer (DFU) is a severe chronic diabetes mellitus complication with delayed wound healing. A number of factors such as antibiotic-resistant bacterial infection, ischemia, matrix metalloproteinases (MMPs)- mediated degradation of granulating tissue, fibroblast senescence and hypoalbuminemia contribute to the severity of DFU. Present therapies are often found to be inactive since they fail to provide a comprehensive solution. To address this challenge, here we have hypothesized that a novel NIR-responsive phototherapeutic complex made with 3d-transition metal ions (preferably Zn²⁺), serum albumin (SA) and indocyanine green (ICG) will effectively work as a multifunctional therapeutic solution for the treatment of DFU. Under exposure to 808 nm Laser, ICG present in the Zn²⁺-SA-ICG complex will generate heat (photothermal effect) and ROS (photodynamic effect) which will kill the antibiotic-resistant bacteria in the wound milieu, Zn²⁺ released from the complex will activate the endothelial cells and help in angiogenesis, and SA will serve as a sacrificial substrate to nullify the degrading effect of MMPs and will activate fibroblast and compensate the hypoalbuminemia. The hypothesis can be tested through a series of biophysical experiments, in vitro microbial and cellular studies, in vivo analysis in MRSA bacteria-infected wound models in STZ-induced diabetic mice and finally through clinical trials. If successful, a new domain of clinical management for DFU will be opened. This will also facilitate the pathway of similar innovation for even better therapy.