A Novel Liposome Capturing Pore-Forming Toxins for the Treatment of Bacterial Infections

Abstract

Pore-forming toxins (PFTs), as the most commonly virulence proteins, are the potent defensive or aggressive "weapons" in multiple bacterial infections. To reduce their damage to the host cells and lighten the degree of bacterial infections, it is a crucial step to remove PFTs in the process of treatment. Based on the pore-forming priciple between PFTs and the membrane of animal cells, we artificially prepared a novel broad-spectrum nanoantidote liposome (called the CSPL), which was composed by natural membrane components existing in human cells. High-concentration and abundant ingredient for toxin-binding as well as the favourable liquidity of CSPL itself guaranteed the forceful affinity for PFTs. With α-toxin as the model of PFTs, CSPL displayed powerful absorbing efficacy in vitro. In addition, CSPL demonstrated notable treatment efficiency in staphylococcus aureus infections in vivo. Finally, we developed vancomycin-loaded CSPL (Van@CSPL), in which the Van can be released at the infectious site through the transmembrane pores in the membrane of CSPL. Therefore, this functionalized integrative platform with detoxification/drug release was able to protect from severe invasive infections in mice. This safe and effective CSPL provides a new strategy for improving the treatment of bacterial infections.