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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: 1.7 ns 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.

Herein we report synthesis of new steroidal oxadiazinanones from steroidal ketones. After characterization by spectral and analytical data, the interaction studies of compounds (4–6) with DNA were carried out by UV–vis, fluorescence spectroscopy and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 1.8 × 104 M−1, 2.2 × 104 M−1 and 2.6 × 104 M−1, respectively, indicating the higher binding affinity of compound 6 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compound 6 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. Molecular simulations suggest that compounds binds through minor groove of DNA. MTT assay depicted promising anticancer activity of compound 5 and 6 particularly against HL-60 and MCF-7. The apoptotic degradation of DNA was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). The results revealed that compound 6 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.