Functional validation of chimeric drug delivery vehicle using various cell lines
Student name: Mr Nipanshu Agarwal
Guide: Dr Udit Soni
Year of completion: 2015
Host Organisation: The Energy and Resources Institute (TERI), New Delhi
Supervisor (Host Organisation): Dr Subhash Chandra Yadav
Abstract: Virus based drug delivery vehicles to deliver the genes are well known but the development of drug delivery vehicles using plant virion (only assembled capsid) by in vitro assembly and capsid bioconjugated ligands (such as CFSE dye for fluorescence, Folic acid for targeting and doxorubicin for activity) showed good potential for targeted delivery of drugs to subcutaneous cancer cells. To validate the targeting ability of CCMV capsid scaffold DDS, we designed experiments to study internalization kinetics in macrophage cells (J774), MCF-7 cells and HEK cells. Macrophages were selected for the evaluation of optimum time for the maximum internalization of DDS. The FR+ MCF-7 cell lines and FR- HEK cell lines were used to qualitatively (by confocal microscopy) and quantitatively (by Fluorimetry) confirm the targeting potential of developed DDS. Folate receptor of MCF-7 cells were also blocked by adding excess of folic acid in culture medium and high reduction in internalization of DDS provide the extra evidence of good targeting potential. This DDS showed folate receptor mediated endocytosis and specific internalization which proves its targeting ability with little cytotoxicity. Hence, this work reveals the potential developed DDS to be used as delivery vehicle for subcutaneous cancer in vivo models.
Key words: Targeted drug delivery system, anti- cancer, Nano scaffold, internalization kinetics, Folate receptor, MCF-7 cell line, HEK cell line, Macrophage cell line (J774).