Infection microenvironment-activated core-shell nanoassemblies for photothermal/chemodynamic synergistic wound therapy and multimodal imaging

Abstract

The development of intelligent designs of new antibacterial modalities for diagnosing and treating chronic multidrug-resistant bacterial infections is an urgent need, but achieving the precisive theranostic in response to specific inflammatory microenvironments remains a great challenge. This paper describes our work designing and demonstrating infection microenvironment-activated core-shell Gd-doped Bi₂S₃@Cu(II) boron imidazolate framework (Bi₂S₃:Gd@Cu-BIF) nanoassemblies. Upon exposure to a single beam of 808 nm laser, Bi₂S₃:Gd@Cu-BIF nanoassemblies showed exceptional photothermal conversion (η = 52.6%) and produced several cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, by depleting the intracellular glutathione and in-situ catalyzing the decomposition of endogenous hydrogen peroxide in the inflammatory microenvironment. The broad-spectrum antibacterial properties of nanoassemblies were confirmed to be effective against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition rate of 99.99% in vitro. Additionally, in vivo wound-healing studies revealed that Bi₂S₃:Gd@Cu-BIF nanoassemblies could serve as an effective wound spray to accelerate healing following MRSA infections via photothermal/chemodynamic (PTT/CDT) synergistic therapy. The effective wound healing rate in the synergistic treatment group was 99.8%, which is higher than the 69.5% wound healing rate in the control group. Furthermore, magnetic resonance and computed tomography dual-modal imaging mediated by Bi₂S₃:Gd@Cu-BIF nanoassemblies also exhibits promising potential as an integrated diagnostic nanoplatform. Overall, this work provides useful insights for developing all-in-one theranostic nanoplatforms for clinical treatment of drug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: New treatments and effective diagnostic strategies are critical for fighting drug-resistant bacterial infections. Infection microenvironment-activated Bi₂S₃@Cu-BIF nanoassemblies can simultaneously increase eigen temperature and generate cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under near-infrared laser irradiation, achieving the synergistic effect of photothermal and chemodynamic therapy, which has been proven to be highly effective for inhibiting bacterial activity and speeding wound healing from methicillin-resistant Staphylococcus aureus infection. More importantly, the nanoassemblies could enable early precise visualized detection of bacterial abscess using magnetic resonance/computed tomography dual-modal bio-imaging techniques.

Keywords: Bacterial infection; Chemodynamic therapy; Photothermal therapy; Theranostic nanoplatforms; Wound healing.