Asialoglycoprotein receptor-1 mediated targeted drug delivery to liver cancer cells using stimuli responsive galactosylated electrospun nanofibers

Synthesis of core–shell nanofiber (DOX@Gal-PVA/NSC) with galactose decorated poly(vinyl alcohol) as shell and doxorubicin loaded N-succinyl chitosan as core was achieved via coaxial electrospinning for site-specific targeting of liver cancer cells. Nanofibers of diameter 200 nm decorated with galactose were realised by in-situ photopolymerization during electrospinning. The galactose confers specific binding to asialoglycoprotein receptor-1 (ASGPR-1), overexpressed on hepatocellular carcinoma cells. The DOX loaded NSC core enable pH-responsive drug release, with higher rate of release to tumor microenvironment thereby increasing the therapeutic efficacy. Hemocompatibility tests demonstrated negligible hemolysis, there by supporting potential in-vivo safety. FITC labelled fibers showed specificity towards the ASGPR-1 receptor and its entry via endosomal uptake pathway facilitated the understanding of organelle trafficking. In-vitro cytotoxicity assays against ASGPR-1 positive liver cancer cells yielded IC₅₀ values of 58.5 μg/mL at 48 h and 6.14 μg/mL at 72 h, indicating enhanced efficacy over time due to sustained DOX release. Nanofibers synthesized using NSC, a derivative of FDA-approved natural polysaccharide, chitosan, renders the platform cost-effective and scalable. Collectively, DOX@Gal-PVA/NSC nanofiber demonstrates targeted and stimuli-responsive drug delivery, exhibiting antitumor activity, warranting promising investigation for hepatocellular carcinoma therapy.