GCGA-siPAK1

GCGA-siPAK1 is a dual-ligand targeted nanoparticle-based gene therapy designed for the treatment of hepatocellular carcinoma (HCC). The drug consists of nanoparticles engineered with two targeting ligands (galactosyl and lactosyl groups) to facilitate specific uptake by HCC cells, exploiting the overexpression of asialoglycoprotein receptor (ASGP-R) and galactose receptor (GA-R) on tumor cell surfaces. The nanoparticles encapsulate and deliver small interfering RNA (siRNA) targeting PAK1 (p21-activated kinase 1) mRNA. Upon intravenous injection, the nanoparticles accumulate in tumors via the enhanced permeability and retention (EPR) effect and are further internalized by ligand–receptor-mediated endocytosis. Once inside the target cells, the siRNA is released, leading to sequence-specific silencing of PAK1 expression, resulting in inhibition of tumor cell proliferation, invasion, migration, and promotion of apoptosis. Preclinical studies demonstrate maximal anti-tumor efficacy for the dual-ligand system, with enhanced cell targeting and therapeutic benefits compared to single-ligand or non-targeted approaches[1][3][5].