Abstract
With high morbidity and death rates, liver cancer has become one of the most common cancers in the world. But, most chemotherapeutic anticancer drugs have high toxicity as well as low specificity. To improve the treatment modalities and enhance the therapeutic effect of liver cancer, a brand new liver-targeting nanoparticle (NP), Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5 F)-loaded cholic acid (CA)-functionalized star-shaped poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-lactobionic acid (LA) (5 F-loaded CA-PLGA-PEG-LA), was developed. The particle size, zeta potential, size distribution, surface morphology, drug loading content, drug encapsulation efficiency and drug release of 5 F-loaded NPs were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be internalized by HepG2 cells. Furthermore, the cellular uptake efficiency of coumarin 6-loaded CA-PLGA-PEG-LA NPs was much better in compare with that of CA-PLGA-PEG and CA-PLGA NPs. Moreover, LA-conjugated NPs (CA-PLGA-PEG-LA NPs) enhanced fluorescence of HepG2 cells via ligand-mediated endocytosis. The antitumor effects of 5 F-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted 5 F-loaded CA-PLGA-PEG-LA NPs were significantly superior to free 5 F and 5 F-loaded CA-PLGA-PEG NPs. All the results indicated the 5 F-loaded CA-PLGA-PEG-LA NPs can be employed as a novel potentially targeting drug delivery system for liver cancer therapy.
Highlights
As one of the most common cancers, liver cancer shows high incidence and mortality rates, especially in less developed countries (Tao et al, 2014; Torre et al, 2015; Yang et al, 2018)
Coumarin 6 (C6), a model fluorescent maker, was encapsulated in the cholic acid (CA)-PLGA NPs, CA-PLGA-polyethylene glycol (PEG) NPs, and CA-PLGAPEG-lactobionic acid (LA) NPs to investigate the uptake by HepG2 cells
The hydrodynamic sizes of NPs synthesized in our study were 100–170 nm, which is within the optimal size range for cellular uptake (Padhi et al, 2018)
Summary
As one of the most common cancers, liver cancer shows high incidence and mortality rates, especially in less developed countries (Tao et al, 2014; Torre et al, 2015; Yang et al, 2018). Previous studies have shown NPs conjugating galactose residues or lactose moieties can effectively and target the sites of hepatoma tumor through the ASGP receptor-mediated recognition (Liang et al, 2006; Craparo et al, 2014; Iacobazzi et al, 2017; Tsend-Ayush et al, 2017). The linear PLGA-PEG NPs have been studied as drug delivery vehicle by many researchers, star-shaped copolymers have attracted a great deal of research interest because of excellent properties. 5 Floaded CA-PLGA-PEG NPs, the star-shaped amphiphilic block copolymers, were surface-modified with LA, a ligand whose galactosyl residue couples with the asialoglycoprotein receptor (ASGPR), allowing the targeted delivery of drugs to liver cancer cells. LC, EE, morphology, in vitro drug release behavior, in vitro cellular uptake, and cytotoxicity of the NPs were tested
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