Treating intracellular Mycobacterial tuberculosis (Mtb) infection is very challenging as Mtb can develop defense mechanisms against immune cells. Here, we reported new strategies to eradicate intracellular pathogenic bacteria from within the cell by developing host-targeted nanotherapeutics (HTNs). The fabrication of a host targeted nano-therapy consisting liposomal hybrid gold nano-assembly with photothermal activity. The core components of the nano assembly include gold nanorods (GNR) coated with mesoporous silica shell (GM) that offers an excellent drug loading surface for encapsulation of drug of choice bedaquiline (GM@BQ). Thermo-sensitive liposome was prepared and host targeting ligand β- Glucan were conjugated on surface of liposome (L-Glu). To avoid premature drug release, GM@BQ was loaded inside liposome tagged host targeting ligand and final nano-assemblies were abbreviated as (GM@BQ)L-Glu or HTNs. The host targeting approach of HTNs leads to enhanced cellular uptake and enhances reactive oxygen species (ROS), reactive nitrogen species (RNS) after binding to dectin-1 receptor present on cell surface. Then, the exposure of near-infrared (NIR) laser irradiation can trigger photothermal-induced structural disruption of nano-assembly, which is helpful for the precise and controllable release of BQ at targeted sites. These released BQ promoting phagosome acidification by recruiting VATPase pump and phagolysosome formation which kill intracellular Mtb. Finally, HTNs trigger apoptosis of Mtb infected macrophages via photothermal therapy (PTT) which prevent further spreading of bacteria. This study offers an appealing candidate that holds great promise for treating intracellular bacterial infections.

Host targeted multifunctional nano-therapy for eradication of intracellular bacterial infection

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.