PREPARATION OF TUMOR TARGETING COMBINATORIAL THERAPY USING NANOPARTICLE CONJUGATED NATURAL COMPOUNDS

Abstract

Cancer, a multifactorial disease, caused by several genetic and environmental factors and their interactions in which normal cells become progressively transformed to malignant cells, is currently the most studied topic. Numerous receptors and pathways have been identified for cancer that play a crucial role in its progression. Natural compounds obtained from various medicinal plants have shown a promising potential in targeting cancer in multiple ways. In the present project we are exploring the design of a combinatorial cancer therapy. At first, different bioactive compounds were screened using literature reviews and researches conducted previously and molecular docking simulations were performed against different receptors involved in cancer associated pathways, particularly breast cancer as India’s most prevalent cancer. In this project, AutoDock was used for molecular docking and later, PyMol 2.3.2 was used for identifying the binding amino acid residues of ligands against targeting receptors. From the results conducted, the binding energies were assessed and it is hereby proposed that, combination of Withferin A, Curcumin, Rutin and Selicib shows highest binding energies against selected key receptors in breast cancer, which can be further explored for combinatorial efficacy. Furthermore, for effective drug delivery, BSA nanoparticles were designed using desolvation process in which the effective size was found to be 160nm with a charge of -100mV. Thus this project holds significant implications for the development of combinatorial therapy using natural compounds and designing new protocols for their in-vivo delivery using nanoparticles, which eventually may have exciting potential for applicability in various cancers.