A multi-targeted nanoconjugate for light-driven therapy of chronic wounds

Abstract

The pathogenic bacteria-induced diabetic ulcer becomes a life-threatening miscellaneous disease and remains a pivotal clinical challenge due to poor healing. To overcome the obstacle, we developed a non-antibiotic strategy based on a three-dimensional multi-targeted nanostructure with near-infrared laser induced photothermal therapy for promoting the healing of diabetic wound infected by Pseudomonas aeruginosa and Staphylococcus aureus. This nanoconjugate was prepared by integrating gold nanorods decorated with bacterial affinitive molecules phenylboronic acid and pH-induced charge-convertible tertiary-amine group. In addition to the binding with the cell wall of bacteria from phenylboronic acid motifs, a dedicated charge conversion of the nanoconjugate from negative charge to positive charge in the acidic microenvironment of bacterial infectious sites further provides robust targeting to negatively charged bacteria. This nanoconjugate could target and kill specific bacterial cells using photothermal ablation. Following excitation by near-infrared light, gold nanorods release energy through nonradioactive decay pathways, locally generating heat that efficiently kills targeted bacterial cells and finally accelerating the wound healing of diabetic rats by down-regulating the expression of proinflammatory factors. Collectively, this nanostructure evolved targeting strategy with the photothermal property is expected to be other kind of treatment programs for repairing chronic wounds of diabetic ulcers infected by multiple bacteria.