Size Dependency of Selective Cellular Uptake of Epigallocatechin Gallate-modified Gold Nanoparticles for Effective Radiosensitization

Abstract

The high incidence and mortality of cancer make it a global health issue. However, conventional cancer therapies have several disadvantages, especially serious side effects due to low selective toxicity to cancer cells. Gold nanoparticles (AuNPs) are an excellent drug carrier, enhance drug delivery efficiency, and hold promise for photothermal and radiation therapies. (−)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic antioxidant constituent of green tea, has a potent antitumor effect, and binds specifically to the 67 kDa laminin receptor, which is overexpressed on the surface of several cancer cell lines such as HeLa and MDA-MB-231 cells. We synthesized EGCG-modified AuNPs (EGCG-AuNPs) using ratios (n EGCG/n gold) from 1:2 to 10:1 and evaluated their size, morphology, stability, antioxidant ability, cytotoxicity, cellular uptake, and uptake mechanisms in vitro in comparison with the conventional AuNPs prepared by using citrate as the reducing agent (citrate-AuNPs). In HeLa cells, EGCG-AuNPs (10:1) (135 nm diameter, sea-urchin-like shape) exhibited the highest cellular uptake. Conversely, EGCG-AuNPs (1:2) (39 nm diameter, spherical shape) were preferentially taken up by MDA-MB-231 cells. Cellular uptake of EGCG-AuNPs toward normal cells (NIH3T3 cells) was found to be in a nonspecific manner, and the amount of uptake was suppressed. X-ray irradiation after cellular uptake of EGCG-AuNPs (1:2) in MDA-MB-231 cells significantly enhanced irradiation-induced cell death. These findings suggest enhanced cellular uptake of EGCG-AuNPs with a 39 nm diameter and their potential use in combinatorial therapeutics of EGCG-AuNPs for breast cancer.

Cellular Uptake of Epigallocatechin Gallate in Comparison to Its Major Oxidation Products and Their Antioxidant Capacity In Vitro

“…Other studies indicate a stronger cellular uptake of EGCG through the use of carrier nanoparticles [ 24 , 25 ]. In addition, liposomes can be superficially modified to increase EGCG cellular uptake [ 23 , 26 ].…”

Nanoformulation Safety versus Toxicity; What do the Recent Studies Tell Us?

“…So, the cellular uptake of AuNPs was seriously dependent on their size. AuNPs toxicity is linked with other properties and the size, including surface modification and particle shape [27].…”

The applications of epigallocatechin gallate (EGCG)-nanogold conjugate in cancer therapy

“…Among nanoparticles, the gold's inertness, non-toxicity and facile surface manipulation enable it to form drug-nanogold conjugates that can be utilized for drug delivery. Another advantage of nanogold is its surface plasmon resonance, which can kill cancer cells due to its size and shape-dependent light-heat conversion capability, potentially opening the door to photodynamic and combination therapies [59][60][61][62][63][64][65][66][67][68][69][70]. The nanogold can be used as an effective nanocarrier for EGCG, increasing the bioavailability and stability significantly [62][63][64][65][66][67][68].…”

“…Another advantage of nanogold is its surface plasmon resonance, which can kill cancer cells due to its size and shape-dependent light-heat conversion capability, potentially opening the door to photodynamic and combination therapies [59][60][61][62][63][64][65][66][67][68][69][70]. The nanogold can be used as an effective nanocarrier for EGCG, increasing the bioavailability and stability significantly [62][63][64][65][66][67][68]. Studies also show that using EGCG-nanogold is more effective in eradicating cancer cells.…”