Page 58 - Annual report 2021-22

Annual Report 2021-22 |

Pradeep Kumar

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Pradeep Kumar’s group works towards developing novel methods for delivery of bioactive molecules
to cells.

Delivery of bioactives

Tremendous progress made in the areas of genomics and molecular biology has offered several
exciting possibilities in biomedical sciences including medicine. Initially, gene therapy was started with
its potential in the treatment of inherited life-threatening diseases, however, with time, the focus of
gene therapy has shifted to treat cancers and other infectious diseases. In the field of cancer therapy,
gene therapy has shown promising potential as it offers a high degree of tumor selectivity compared
to the conventional chemotherapeutic approaches. For an efficient gene transfer to a tumor site,
delivered DNA has to cross several barriers enroute to the nucleus of the target cell. Due to the
vulnerability of DNA to intra- and extracellular nucleases, large size and negative charge, effective
applications of DNA in cancer gene therapy are of limited value. Therefore, suitable carrier systems
are required to improve DNA transfer efficacy. During this period, Pradeep Kumar’s group is engaged
in developing safe and efficient newer strategies for in vitro delivery of nucleic acids to cancer cell
lines. Two different types of conjugates with low and high molecular weight polyethylenimine were
synthesized, characterized by spectroscopic techniques and evaluated for anticancer potential in
several cancer cells. In one of the approaches, a series of amphiphilic retinoyl-bPEI conjugates has
been synthesized by allowing the reaction between bPEI and a bioactive and hydrophobic vitamin A
metabolite, retinoic acid, which acts as an endogenous ligand for retinoic acid receptors (RARs) that
regulate target gene expression leading to cell differentiation, decreased cell proliferation and
inhibition of tumorigenesis, in varying amounts. In aqueous medium, these conjugates self-assemble
into core-shell RP nanocomposites. Due to anticancer activity of retinoic acid, DNA-RP complexes
significantly reduced the viability of cancer cells (HepG2 and MCF-7 cells) without affecting the viability
of non-cancerous cells (HEK293 cells) demonstrating the cell-selective nature of the formulated
nanocomposites. The results demonstrated the promising potential of the RP conjugates that can be
used in future hepatocellular carcinoma targeted gene delivery applications. In another approach, the
group synthesized trehalose-PEI organic nanoparticles and evaluated their potential in delivering the
nucleic acids in vitro. Transfection efficiency exhibited by DNA complexes was significantly higher than
the unmodified polymer and the standard, Lipofectamine complexes. Trehalose-PEI organic
nanoparticles (TPONs) exhibited greater pDNA transportation potential and also showed promising
anticancer activity on cancer cell lines i.e. Mg63, MCF-7 and HepG2. Overall, trehalose-PEI organic
nanoparticles hold considerable potential to be used in various biomedical applications as promising
delivery, anti-cancer and anti-oxidative agents.