Epigallocatechin Gallate Potentiates the Anticancer Effect of AFP-siRNA-Loaded Polymeric Nanoparticles on Hepatocellular Carcinoma Cells

Abstract

To develop a potential cancer treatment, we formulated a novel drug delivery platform made of poly(lactic-co-glycolic) acid (PLGA) and used a combination of an emerging siRNA technology and an extracted natural substance called catechins. The synthesized materials were characterized to determine their properties, including morphology, hydrodynamic size, charge, particle stability, and drug release profile. The therapeutic effect of AFP-siRNA and epigallocatechin gallate (EGCG) was revealed to have remarkable cytotoxicity towards HepG2 when in soluble formulation. Notably, the killing effect was enhanced by the co-treatment of AFP-siRNA-loaded PLGA and EGCG. Cell viability significantly dropped to 59.73 ± 6.95% after treatment with 12.50 μg/mL of EGCG and AFP-siRNA-PLGA. Meanwhile, 80% of viable cells were observed after treatment with monotherapy. The reduction in the survival of cells is a clear indication of the complementary action of both active EGCG and AFP-siRNA-loaded PLGA. The corresponding cell death was involved in apoptosis, as evidenced by the increased caspase-3/7 activity. The combined treatment exhibited a 2.5-fold increase in caspase-3/7 activity. Moreover, the nanoparticles were internalized by HepG2 in a time-dependent manner, indicating the appropriate use of PLGA as a carrier. Accordingly, a combined system is an effective therapeutic strategy.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma

“…For instance, using small interfering RNA (siRNA) or antisense oligonucleotides (ASO) technology to reduce AFP expression. These technologies can specifically inhibit the synthesis of AFP or prevent its interaction with target cells, thereby suppressing tumor growth and diffusion ( 96 , 97 ). Secondly, the use of recombinant AFP, combined with anticancer drugs, has been widely explored.…”