GSH Responsive Norbornene – based Site Specific Mitochondria Targeting Drug Delivery For Cancer Theranostics

Kemprai, Chaarvi (2025) GSH Responsive Norbornene – based Site Specific Mitochondria Targeting Drug Delivery For Cancer Theranostics. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Chaarvi Kemprai (20MS061)) 20MS061_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (4MB)

Abstract

Cancer continues to pose a significant global health challenge, with current therapies often restricted due to insufficient selectivity, systemic toxicity, and the development of multidrug resistance. To tackle these issues, this thesis introduces the creation of a novel glutathione (GSH)-responsive polymeric nanocarrier based on norbornene, aimed at achieving site-specific and mitochondria-targeted drug delivery for cancer theranostics. The approach of this thesis includes the synthesis of three functional monomers: (1) a norbornene derivative with disulfide bonds for redox-responsiveness, (2) a hydrophobic monomer that facilitates self-assembly into micelles (3) a PEG-functionalized monomer that ensures solubility and stealth properties. These monomers were copolymerized through Ring-Opening Metathesis Polymerization (ROMP) utilizing the Grubbs 3rd Generation (G3) catalyst to create an amphiphilic random copolymer characterized by well-defined molecular weight and narrow polydispersity. The polymer was analyzed using Advanced Polymer Chromatography (APC), which confirmed the successful formation of the copolymer, revealing a number-average molecular weight of around 43.5 Da and a PDI of approximately 1.12. The redox-responsiveness of the system was demonstrated through time-dependent UV-Vis and fluorescence spectroscopy, indicating activation triggered by GSH.

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