A Sodium Alginate-Based Multifunctional Nanoplatform for Synergistic Chemo-Immunotherapy of Hepatocellular Carcinoma.

Efficient hepatocellular carcinoma (HCC) treatment remains a significant challenge due to the inherent limitations of traditional strategies. The exploration of polysaccharides' natural immunity for immunotherapy of HCC has been rarely explored. For this purpose, we reported in this study facile construction of a multifunctional nanoplatform, biotinylated aldehyde alginate-doxorubicin nano micelle (BEA-C = N-DOX-M) for synergistic chemo-immunotherapy by the use of constant β-D-mannuronic acid (M) units and modulated α-L-guluronic acid (G) units in the alginate (ALG) structure. The constant M units show natural immunity and specific binding ability with mannose receptor (MR) via strong receptor-ligand interactions, and the modulated G units serve as highly reactive conjugation sites for biotin (Bio) and DOX. This formulation not only integrates natural immunity of ALG and ICD triggering function of DOX, but also shows dual targeting properties to HCC cells via MR and Bio receptor (BR)-mediated endocytosis pathways. Notably, BEA-C = N-DOX-M at an equivalent dose of 3 mg/kg of DOX mediated tumor inhibitory efficiency 12.10% and 4.70% higher than free DOX and aldehyde alginate-doxorubicin nano micelle (ASA-C = N-DOX-M), respectively, in Hepa1-6 tumor-bearing mice. This study reported the first example of integrating natural immunity of ALG and ICD effect of anticancer drugs for enhanced chemo-immunotherapy of HCC. This article is protected by copyright. All rights reserved.