Dual Oxygen Supply System of Carbon Dot-Loaded Microbubbles with Acoustic Cavitation for Enhanced Sonodynamic Therapy in Diabetic Wound Healing

Abstract

Diabetic wounds present significant treatment challenges due to their complex microenvironment, marked by persistent inflammation from bacterial infections, hypoxia caused by diabetic microangiopathy, and biofilm colonization. Sonodynamic therapy (SDT) offers potential for treating such wounds by targeting deep tissues with antibacterial effects, but its efficacy is limited by hypoxic conditions and biofilm barriers. To overcome these obstacles, we developed a novel approach using oxygen-carrying microbubbles loaded with Mn2+-doped carbon dots (MnCDs@O2MBs) to enhance SDT and disrupt biofilms. Through precursor screening and design, MnCDs are engineered to exhibit tailored properties of sonodynamic activity and enzyme-like catalytic capabilities. This system provides a dual oxygen supply for amplifying the SDT effects: MnCDs, serving as a sonosensitizer, also chemically convert excess H2O2 at infection sites into oxygen, while the O2MBs physically release oxygen through ultrasound-induced cavitation. The cavitation effect also disrupts biofilms, improving the delivery of sonosensitizers and boosting SDT efficacy. In a diabetic wound model, this strategy downregulated TLR, NF-κB, and TNF inflammatory pathways, reduced pro-inflammatory factor secretion, promoted angiogenesis, and accelerated wound healing, thereby acting as a promising treatment approach for diabetic wound healing.

Keywords: Diabetic wounds, carbon dots, sonodynamic therapy, dual oxygen supply, cavitation.