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

Abstract

Efficient hepatocellular carcinoma (HCC) treatment remains a significant challenge due to the inherent limitations of traditional strategies. The exploration of polysaccharides’ natural immunity for HCC immunotherapy is rarely explored. For this purpose, facile construction of a multifunctional nanoplatform, biotinylated aldehyde alginate‐doxorubicin nano micelle (BEACNDOXM) is reported in this study for synergistic chemo‐immunotherapy by using constant β‐D‐mannuronic acid (M) units and modulated α‐L‐guluronic acid (G) units in the alginate (ALG) structure. The M units show natural immunity and specific binding ability with mannose receptors (MRs) via strong receptor‐ligand interactions, and the G units serve as highly reactive conjugation sites for biotin (Bio) and DOX. Therefore, this formulation not only integrates the natural immunity of ALG and the immunogenic cell death (ICD) triggering function of DOX, but also shows dual targeting properties to HCC cells via MRs and Bio receptors (BRs)‐mediated endocytosis. Notably, BEACNDOXM mediates a tumor inhibitory efficiency 12.10% and 4.70% higher than free DOX and single targeting aldehyde alginate‐doxorubicin nano micelle controls, respectively, at an equivalent DOX dose of 3 mg kg−1 in Hepa1‐6 tumor‐bearing mice. This study reports the first example of integrating the natural immunity of ALG and the ICD effect of anticancer drugs for enhanced chemo‐immunotherapy of HCC.

Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity

“…Moreover, ICG also can stimulate tumor cells to release damage-associated molecular patterns to induce immunogenic cell death (ICD), which promotes dendritic cell (DC) maturation and amplifies T cell infiltration for immunotherapy [27][28][29][30][31]. The traditional first-line chemotherapy agent doxorubicin (DOX) could also trigger ICD-mediated immune responses [32][33][34][35][36]. Additionally, Yang et al designed a DOX/ICG-loaded nanoscale ZIF-8 formation, which targeted tumors for synergistic tumor therapy [37].…”

Carrier-Free Self-Assembled Nanomedicines for Promoting Apoptosis and Inhibiting Proliferation in Hepatocellular Carcinoma

“…Nanoparticles (NPs) selectively deliver therapeutic drugs to tumors for multimodal treatment of tumors through enhanced permeability and retention (EPR) effects. , Compared to small molecules, nanomedicines are able to improve therapeutic efficiency at lower doses and increase the bioavailability of the drug, thereby reducing side effects on normal organs. , With the help of nanocarriers, nanopharmaceutical formulations realize the above advantages. However, most of the nanocarriers used for loading drugs exhibit very low loading capacity because the nanocarriers themselves account for a much larger proportion of the nanoparticles than the drug. , In addition, the preparation of nanocarriers is a complex, hazardous, and energy-consuming process, including the use of organic solvents, high temperatures and pressures required for synthesis, and so on, which may lead to quality problems due to the variations in the process from batch to batch. , Self-assembled nanoparticles have the advantages of nanoscale drug delivery systems and a high drug loading capacity.…”

Self-Assembly Reinforced Alginate Fibers for Enhanced Strength, Toughness, and Bone Regeneration

“…Naturally abundant sodium alginate (SA) is a linear polysaccharide extracted from brown seaweeds . The molecular units of β-D-mannuronic acid (M unit) and α-L-guluronic acid (G unit) ensure SA free of neurotoxicity, good biocompatibility, and biodegradability. − These features endow alginate fibers excellent characteristics including skin-friendliness, moisture absorption, antibacterial, as well as renewability. , Alginate fibers become ideal candidates for rapid wound healing, cosmetics, environmental protection, tumor therapy, and other fields. − Compared with other biobased fibers, the relatively lower mechanical property limits their applications.…”