Proposal Defense – Vikrantvir Jain

About the event

Speaker: Vikrantvir Jain

Group: Dr. Anjali Sharma

Title: Nanotherapeutics for Targeted and Effective Liver-Specific Drug Delivery

Abstract: Dendrimers are highly branched, nanoscale polymers with a defined architecture and multiple functional groups that enable the attachment of drugs, targeting ligands, and imaging agents. Their structural versatility makes them ideal nanocarriers for overcoming the limitations of conventional liver disease therapies, including poor site-specific delivery, systemic toxicity, and subtherapeutic drug concentrations. This proposal focuses on the development of galactose-functionalized dendrimers (Gal24) that exploit the asialoglycoprotein receptor (ASGPR) abundantly expressed on hepatocytes and hepatic cancer cells for selective liver targeting and intracellular delivery. Aim 1 involves the development of Silibinin-conjugated Gal24 dendrimers (Gal24-Sil) for targeted drug delivery to hepatocellular carcinoma (HCC) cells. Silibinin, a hepatoprotective flavonoid with antioxidant, anti-inflammatory, and anticancer properties, will be conjugated to Gal24 using efficient click chemistry to ensure scalability and reproducibility. The synthesized conjugates and their fluorescent derivatives will be evaluated for hepatocyte-specific targeting and enhanced therapeutic efficacy in HepG2 and Hep3B models of HCC. Aim 2 focuses on creating a dual-targeting system by conjugating triphenylphosphine (TPP) and Sorafenib (Sora) to Gal24 dendrimer (Gal24-TPP-Sora) for mitochondria-specific drug delivery in HCC treatment. Sorafenib, a frontline therapy for advanced HCC, is limited by poor solubility, low bioavailability, and drug resistance. Incorporation of TPP, a mitochondria-targeting moiety, enables both hepatocyte-specific uptake and mitochondrial accumulation, enhancing drug localization, promoting apoptosis, and minimizing systemic toxicity. Overall, this work aims to establish a multifunctional dendrimer nanoplatforms for targeted drug delivery in HCC, offering a promising strategy to improve therapeutic efficacy and safety in the treatment of HCC and related liver disorders.