In Vitro and in Vivo Evaluation of Pectin-Based Nanoparticles for Hepatocellular Carcinoma Drug Chemotherapy

Abstract

The fabrication and evaluation of a natural pectin-based drug delivery system are reported in this study. The drug delivery system displays specific active targeting ability to hepatocellular carcinoma due to the presence of excess galactose residues in the polymer structure as the natural targeting ligands. The system was prepared under very mild conditions in an aqueous medium containing Ca(2+) and CO3(2-) ions, generating uniform pectin-based nanoparticles with an average diameter of 300 nm, and the drug-loading content of anticancer drug 5-fluorouracil (5-FU) is around 24.8%. Cytotoxicity study of the 5-FU-loaded nanoparticles (5-FU-NPs) in HepG2 and A549 cell lines demonstrated their greater potency in killing cancer cells with overexpressed asialoglycoprotein receptor (ASGPR) on the cell surface, compared to that of the free drug. Pharmacokinetics study using Sprague-Dawley (SD) rats further confirmed that the drug-loaded nanoparticles showed a much longer half-life in the circulation fluids than the free drug. Tissue distribution was investigated on Kunming mice, and the results also demonstrated that the 5-FU-NPs has a long circulation effect. Taken together, the pectin-based drug delivery systems exhibit size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines; therefore, it is a promising platform for the treatment of hepatocellular carcinoma.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…Recently, in vitro and in vivo evaluation of pectinate NPs loaded with anticancer drug 5-fluorouracil (5-FU) for HCC was carried out, and the pectin served as drug delivery vector of chemotherapy agent and natural targeting ligand to ASGPR in this NTDDS. 91 The content of 5-FU in HepG2 cells incubated with the nano-system was significantly higher than that in cells treated with free 5-FU due to the high efficiency of NTDDS. The ASGPR-mediated recognition and subsequent endocytosis of pectinate NPs was proved by blocking the ASGPR on HepG2 cells by free Gal, indicating that it is a promising platform for targeted therapy of HCC through specific binding of galacturonic acid residues of pectin and ASGPR on hepatoma cells.…”

“…Pectin, another polysaccharide with anion, water solubility, and non-toxicity, has attracted attention for targeted therapy in HCC. [89][90][91] It is a natural linear polymer mainly consisting of α-(1-4)-linked d-polygalacturonic acid residues in Figure 4 and extracted from citrus peels or apple pomaces. The d-polygalacturonic acid is an oxidized form of Gal, thus the pectin displays active targeting ability to hepatoma cells contributing to the specific interaction between galacturonic acid residues and ASGPR on the cells.…”

Encapsulation of honokiol into self-assembled pectin nanoparticles for drug delivery to HepG2 cells

“…Pectin, an important polysaccharide, mainly consists of ␣-(1-4)-linked dpolygalacturonic acid residues (Cheng & Lim, 2004;Fan et al, 2008;Yu et al, 2009). Nanoparticles containing pectin may target hepatocellular carcinoma cells (Chittasupho, Jaturanpinyo, & Mangmool, 2013;Verma & Kumar, 2013;Yu et al, 2014). Nevertheless, pectin nanoparticles are hydrophilic gel nanoparticles and can efficiently encapsulate water-soluble drugs.…”

Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which is ranked fifth in the incidence of malignant tumors and is the third most common cause of cancer-related mortality [1,2] . Different etiologies may be associated with different molecular carcinogenic pathways [3] .…”