Enhanced anticancer activity of (–)-epigallocatechin-3-gallate (EGCG) encapsulated NPs toward colon cancer cell lines

Abstract

(–)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol of green tea, has chemo-preventive effects against various cancer cells. Nanoparticles (NPs) carrying different ligands are able to specifically interact with their receptors on different cancer cells that can provide effective release of cytotoxic drugs. In the present study, we have prepared EGCG entrapped NPs using PLGA (poly(d,l-lactide-co-glycolide)). Polyethylene glycol (PEG) and folic acid (FA) via double emulsion solvent evaporation (DESE) method obtained PLGA-EGCG (P-E), PLGA-PEG-EGCG (PP-E), and PLGA-PEG-FA-EGCG (PPF-E). Nanoformulations had been characterized with ¹H NMR and FT-IR techniques, AFM, and DLS. PPF-E NPs showed an average size of 220 nm. Analysis of zeta potential confirmed the stability of NPs. HCT-116, HT-29, HCT-15, and HEK 293 cells were treated with both the prepared NPs and free EGCG (0–140 μM). Result showed PPF-E NPs had improved delivery, uptake and cell cytotoxicity toward human folic acid receptor-positive (FR+) colorectal cancer (CRC) cells as mainly on HCT-116 compared to HT-29, but not on the folic acid-negative cells (FR−) as HCT-15. PPF-E NPs enhanced intracellular reactive oxygen species (ROS) level in absence of N-acetyl-l-cysteine (NAC), elevated DNA fragmentation level, and increased apoptotic cell death at higher doses compared to other two NPs and free EGCG. In conclusion, PPF-E NPs exerted greater efficacy than PP-E, P-E, and free EGCG in HCT-116 cells.

Graphical Abstract

Represents the synthesis of the PLGA-PEG-FA-EGCG NPs by followed the double emulsion solvent evaporation method that provided the cell cytotoxicity and ultimately cell apoptosis. PLGA first conjugated with PEG di-amine by covalent bond then conjugated with FA in next step to produce PLGA-PEG-FA polymer, then EGCG incorporated to give PLGA-PEG-FA-EGCG NPs. Formulated NPS provided cell cytotoxicity, measured cellular uptake, caused to increase the ROS and caspase 3/9 and also apoptotic proteins that turned ultimately cell apoptosis.

Keywords:

• Polymeric nanoparticles
• folic acid receptor
• reactive oxygen species (ROS)
• apoptosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is supported by the Department of Biotechnology-North Eastern Region (DBT-NER), Government of India.