Near-infrared responsive targeted drug delivery system that offer chemo-photothermal therapy against bacterial infection

To combat the rise of antibiotic resistant bacteria, it is essential to look upon other therapeutic solutions that do not solely depend upon conventional antibiotics. Here, we have designed a combinational therapeutic approach that kills bacteria with the conjunction of photothermal (PT) and antibiotic therapy. A near-infrared (NIR) laser activated targeted drug delivery nano-assembly delivers antibiotic as well as offer PT therapy (PTT). The synergistic application of both therapies increases the efficacy of treatment. The protected delivery of antibiotic and its release in the proximity of the bacteria surface reduces off-target toxicity and reduce the efficacious dosage. Core of the nano-assembly is composed of NIR active gold nanorods (GNRs) coated with a mesoporous silica nanoparticle (MSNP), which serves as a carrier for an anti-tuberculosis drug bedaquiline (BDQ). The assembly was wrapped within a thermo-sensitive liposome (TSL) conjugated to mycobacteria-targeting peptide: NZX, GNR@MSNP@BDQ@TSL@NZX. NZX mediates adhesion of final nano-assembly on mycobacteria surface. Upon NIR laser irradiation GNRs convert photo energy of the laser to localized heat, which melts TSL triggering release of BDQ. Antibacterial activity of final nano-assembly against Mycobacterium smegmatis (Msmeg) was 20 folds more efficacious than the free drug equivalent. The final nano-assembly could also successfully inhibit the growth of intracellular mycobacteria residing in lung cells.