Biofilm Microenvironment-Activated Multimodal Therapy Nanoplatform for Effective Anti-Bacteria and Wound Healing

Abstract

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ ions, CuS along with hydrogen sulfide (H2S) gas. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3% and 99.6% against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing.

Note:
Funding Information: This research was financially supported by the National Natural Science Foundation of China (52250077, and 52272156), and the Taishan Scholars Project (ts20190911).

Declaration of Interests: The authors declare no competing financial interest.

Ethical Approval Statement: All animal experiments were approved by the Ethical Committee of Shandong University under production license number SCXK 2019-0001 and use license number SYXK 2019-0005.

Keywords: H2S gas therapy, multimode synergistic antibacterial, anti-inflammatory, biofilm response