Proposal Defense – Roya Kashfi Sadabad

About the event

Speaker: Roya Kashfi Sadabad

Group: Dr. Anjali Sharma

Title: Development of Nanocarriers for Site-Specific Therapy in Liver disease

Abstract:

Dendrimers are highly branched, nanoscale polymers with precise architecture and abundant surface functional groups that enable the conjugation of therapeutic agents, targeting ligands, and imaging probes. Their structural versatility makes them ideal nanocarriers for addressing the limitations of conventional liver disease therapies, such as poor bioavailability, non-specific distribution, and systemic toxicity. This proposal focuses on the development of N-acetyl galactosamine (GalNAc) and galactose (Gal) functionalized dendrimers (GalNAc-D and Gal-D) designed to exploit the asialoglycoprotein receptors (ASGPR), which are abundantly expressed on hepatocytes and hepatocellular carcinoma (HCC) cells, for receptor-mediated targeting and intracellular delivery. The first aim focuses on the design, synthesis, and comparative evaluation of GalNAc-D and Gal-D to investigate their biocompatibility, hemocompatibility, and cellular uptake in hepatocyte-derived in vitro models (HEK293, HepG2, and Hep3B). These studies will help determine the relative targeting performance of each dendrimer system and identify the most effective nanocarrier for ASGPR-mediated liver-specific delivery. Aim 2 involves the development of a Lenvatinib-conjugated GalNAc dendrimer (GalNAc-D-LEN) for the targeted therapy of HCC. Although Lenvatinib is an approved first-line treatment for advanced HCC, its therapeutic potential is limited by poor solubility, rapid systemic clearance, and dose-dependent toxicity. Covalent conjugation of Lenvatinib to GalNAc-D via click chemistry is expected to enhance its stability, solubility, and selective accumulation in HCC cells while reducing off-target effects.In summary, this work aims to develop a safe and efficient ASGPR-targeted dendrimer platform for liver-specific drug delivery, offering a promising strategy to enhance therapeutic efficacy and reduce systemic toxicity in HCC treatment.