Pijus K. Sasmal

Oxovanadium(IV)-based near-IR PDT agents: Design to biological evaluation

An oxovanadium(IV) complex of dipyridophenazine, as a potent metal-based PDT agent, shows efficient DNA photocleavage activity at near-IR region and high photocytotoxicity in both UV-A and visible light in HeLa cells.

Catalytic Azide Reduction in Biological Environments

In the quest for the identification of catalytic transformations to be used in chemical biology and medicinal chemistry, we identified iron(III) meso‐tetraarylporphines as efficient catalysts for the reduction of aromatic azides to their amines. The reaction uses thiols as reducing agents and tolerates water, air, and other biological components. A caged fluorophore was employed to demonstrate that the reduction can be performed even in living mammalian cells. However, in vivo experiments in nematodes (Caenorhabditis elegans) and zebrafish (Danio rerio) revealed a limitation to this method: the metabolic reduction of aromatic azides.

Single vehicular delivery of siRNA and small molecules to control stem cell differentiation.

Achieving a controlled and reproducible means to direct stem cell differentiation is the single most critical concern scientists have been trying to address since the discovery of stem cells. In this regard, the use of small molecules and RNA interference offers unique advantages by targeting different cellular mechanisms. Our cyclodextrin-modified dendritic polyamine construct (termed DexAM) combines the unique properties of two distinct chemical moieties in a single delivery vehicle. DexAM is a single vehicle that not only solubilizes hydrophobic small molecules in physiological solutions but also forms complexes with siRNA molecules, making it an attractive delivery system for controlling stem cell differentiation. Herein, we report the synthesis and application of DexAM to simultaneously deliver hydrophobic small molecules and siRNA into neural stem cells to significantly enhance their neuronal differentiation.

Photo-triggerable hydrogel–nanoparticle hybrid scaffolds for remotely controlled drug delivery

Remotely-triggerable drug delivery systems enable the user to adjust dosing regimens on-demand based on a patients physiological response and clinical needs. However, currently reported systems are limited by the non-specific leakage of drugs in the absence of triggering and the lack of repeatability over multiple cycles of release. To this end, we have designed a unique hydrogel-nanoparticle hybrid scaffold that provides a chemically-defined, remotely-triggerable and on-demand release of small molecule drugs. Our hybrid platform consists of three distinct components: 1) a photo-triggerable chemical compound, which serves to release a covalently-bound drug upon photo-irradiation, 2) a nanoparticle, which serves to covalently bind the photo-triggerable compound, and 3) a polymeric hydrogel, which serves to hold the drug-conjugated nanoparticle. Upon photo-irradiation, the activation of the photo-triggerable compound is designed to initiate a series of intramolecular chemical rearrangements, which would cleave the covalently-bound drug and release it from the hydrogel. The combination of these distinct components in a single scaffold proved to be an effective drug delivery system, as demonstrated by the delivery of a model drug to a malignant cancer line. Our hybrid scaffold can be easily tuned for practically any biological application of interest, thus offering immense potential for clinical therapies.

Planar triazinium cations from VO2+-assisted ring cyclizations: a remarkably efficient thiazole species for nuclear staining, PDT and anaerobic photocleavage of DNA

Planar triazinium cationic species, from VO(2+)-assisted cyclization of 1-(2-thiazolylazo)-2-naphthol, shows efficient DNA intercalative binding, visible light-induced anaerobic plasmid DNA photocleavage activity and photocytotoxicity in HeLa and MCF-7 cancer cells by an apoptotic pathway with selective localization of the compound in the nucleus as evidenced from the nuclear staining and confocal imaging.