CS-PEG decorated PLGA nano-prototype for delivery of bioactive compounds: A novel approach for induction of apoptosis in HepG2 cell line

Abstract

Purpose: Polymer-based nanoparticles are used as vectors for cancer drug delivery. The bioactive compounds (quercetin, ellagic acid and gallic acid) are well known to be not only antioxidants but also chemopreventive candidates against various types of cancers. To circumvent the low bioavailability and the short half-life time obstacles, we hypothesized a novel PLGA nano-platform functionalized with CS and PEG to encapsulate these phytochemicals. This encapsulation will protect the compounds from the phagocytic uptake and deliver PLGA-CS-PEG nano-prototype with high biodegradability and biosafety.

Materials and methods: Three consequent types of PLGA-based nanocomposites were prepared and characterized. Furthermore, we investigated the newly synthesized nano-formulations against human hepatocellular carcinoma (HepG2) and colorectal cancer (HCT 116) cell lines using cell growth inhibition assays, followed by apoptosis and necrosis assays using flow cytometry to detect the underlying mechanism of HepG2 cell death.

Results: Through Malvern Zeta Sizer, we recorded that the average diameters of the nano-prototypes ranged from 150 to 300nm. The cytotoxic activity of quercetin, ellagic acid, and gallic acid-encapsulated PLGA, PLGA-CS, and PLGA-CS-PEG nano-prototypes it has been found that they reduce the IC50s of the HepG2 cells values by 2.2, 2.9, 2.8-folds, 1, 1.5, 2.7-folds, and 0.9, 0.7, 1.5-folds, respectively. Mechanistically, the nano-platforms of quercetin seem to be dependent on both apoptosis and necrosis, while those of ellagic acid and gallic acid are mainly dependent on apoptosis.

Conclusions: CS-PEG-blended PLGA nano-delivery system of quercetin, ellagic acid and gallic acid can potentiate apoptosis-mediated cell death in HepG2 cell line.

Keywords: Apoptosis; HepG2 cell line; PLGA-CS-PEG nanoparticles; Phytochemicals.