Drug-loaded nanoparticles conjugated with genetically engineered bacteria for cancer therapy

Abstract

Drug-loaded nanoparticles have been widely used as synergists in high-intensity focused ultrasound (HIFU) tumor ablation therapy. However, these synergists have certain limitations, such as poor tumor targeting and low accumulation at the tumor site, that restrict the therapeutic efficacy of HIFU. In this study, we utilized drug-loaded nanoparticles conjugated with genetically engineered bacteria which can selectively colonize the hypoxic areas of tumor to facilitate HIFU ablation. Genetically modified Escherichia coli carrying gas vesicles (GVs-E. coli), which were gas-filled protein nanostructures, had a negatively charged surface and could specifically target into the tumor. In contrast, paclitaxel (PTX) and perfluorohexane (PFH) co-loaded cationic lipid nanoparticles (PTX-CLs) had a positively charged surface, hence, GVs-E. coli was used as a vehicle by conjugating with PTX-CLs via electrostatic adsorption and subsequently attracting more PTX-CLs to the tumor site. To improve the therapeutic efficiency of HIFU, the GVs in GVs-E. coli and PFH encapsulated in PTX-CLs could act as cavitation nuclei to enhance the HIFU cavitation effect, while PTX entrapped in PTX-CLs was released at the tumor site under HIFU irradiation, enhancing the therapeutic efficacy of HIFU and chemo-synergistic therapy. This novel combination strategy has great potential for cancer treatment.