Photoinactivation of multidrug resistant bacteria by monomeric methylene blue conjugated gold nanoparticles

Abstract

Multidrug resistant (MDR) bacterial infections have become a severe threat to the community health due to a progressive rise in antibiotic resistance. Nanoparticle-based photodynamic therapy (PDT) is increasingly been adopted as a potential antimicrobial option, yet the cytotoxicity associated with PDT is quite unspecific. Herein, we show Concanavalin-A (ConA) directed dextran capped gold nanoparticles (GNPDEX-ConA) enhanced the efficacy and selectivity of methylene blue (MB) induced killing of multidrug resistant clinical isolates. Here, we show that our complex MB@GNPDEX-ConA is effective against range of MDR clinical isolates, including Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. In our treatment modality negligible dark toxicity suggests photochemically driven process with 97% killing of MDR bacteria. GNPDEX-ConA with monomeric form of MB departs maximum fluorescence decay time (τf: 1.7ns in HSA) and singlet oxygen (ΔΦ; 0.84) for improved activity in albumin rich infection sites. Further, the complex show least toxicity when tested against HEK293 mammalian cells. The principle component analysis (PCA) and confocal microscopy illustrates cytosolic 1O2 mediated type-II PDT as mechanism of action. Hence, MB@GNPDEX-ConA mediated PDT is potential therapeutic approach against MDR infections and can be tailored to fight other infectious diseases.