Multifaceted mesoporous silica-based nanoplatform to co-deliver honokiol and baicalin for integrative therapy of drug-resistant bacteria infection.

Bacterial infections and excessive inflammation are the main factors that hinder chronic wound healing. The current research mainly focused on killing wound bacteria, but ignoring the excessive inflammation caused by lipopolysaccharide (LPS) released by dead bacteria. Meanwhile, the bacterial cell wall and the bacterial biofilm as a natural barrier for bacteria can strongly block the penetration of antimicrobial drugs. In this study, we designed a multifaceted smart nanoplatform to co-deliver the antibacterial molecule honokiol (HK) as well as the anti-inflammatory molecule baicalin (BA) for synergistic eradication of wound infection. And this multifaceted nanoplatform was composed of fractal mesoporous silica nanoparticles (FSNs) with spiky structure capped by chitosan (CS) as a pH-responsive valve and grafted with folic acid (FA) to achieve specific binding to folate receptors overexpressed on the surface of the bacterial biofilms. Notably, this integrated fractal mesoporous silica-based nanoplatform played a prominent role in enhancing antimicrobial action as well as eliminating the mature biofilm. And under the acidic microenvironment of bacterial infection, this smart nanoplatform could specifically adhere to bacteria, and responsively release both HK and BA. As compared to free drugs (HK and BA) or unmodified FSNs, the fractal mesoporous silica-based nanoplatforms for co-delivery of HK and BA exhibited stronger capacity of biofilm eradication and killing the multidrug-resistant bacteria, and stimulated macrophage polarization toward the M2 phenotype and promote wound healing. Therefore, this multi-stimuli-responsive smart nanoplatform capable of co-delivering dual drugs appears to be a highly promising strategy for integrative therapy, offering efficient antibacterial and long-term anti-inflammatory effects in the treatment of chronic wounds.