Epigallocatechin Gallate-Gold Nanoparticles Exhibit Superior Antitumor Activity Compared to Conventional Gold Nanoparticles: Potential Synergistic Interactions.

Suhash Chavva,Sachin Deshmukh,Seema Singh,Rajashekhar Kanchanapally,Nikhil Tyagi,Jason Coym,Ajay Singh

doi:10.3390/nano9030396

Suhash Chavva, Sachin Deshmukh + Show 5 more

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https://doi.org/10.3390/nano9030396

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Abstract

Epigallocatechin gallate (EGCG) possesses significant antitumor activity and binds to laminin receptors, overexpressed on cancer cells, with high affinity. Gold nanoparticles (GNPs) serve as excellent drug carriers and protect the conjugated drug from enzymatic metabolization. Citrate-gold nanoparticles (C-GNPs) and EGCG-gold nanoparticles (E-GNPs) were synthesized by reduction methods and characterized with UV-visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Cytotoxicity of citrate, EGCG, C-GNPs, and E-GNPs was evaluated by the water-soluble tetrazolium salt (WST-1) assay. Nanoparticle cellular uptake studies were performed by TEM and atomic absorption spectroscopy (AAS). Dialysis method was employed to assess drug release. Cell viability studies showed greater growth inhibition by E-GNPs compared to EGCG or C-GNPs. Cellular uptake studies revealed that, unlike C-GNPs, E-GNPs were taken up more efficiently by cancerous cells than noncancerous cells. We found that E-GNP nanoformulation releases EGCG in a sustained fashion. Furthermore, data showed that E-GNPs induced more apoptosis in cancer cells compared to EGCG and C-GNPs. From the mechanistic standpoint, we observed that E-GNPs inhibited the nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-κB) with greater potency than EGCG, whereas C-GNPs were only minimally effective. Altogether, our data suggest that E-GNPs can serve as potent tumor-selective chemotoxic agents.

Highlights

Cancer is a major public health problem worldwide [1]
PE Annexin V apoptosis detection kit was from BD Bioscience (San Diego, CA, USA); gold (III) chloride trihydrate (HAuCl4·3H2O), trisodium citrate (TSC), and citrate assay kit were from Sigma-Aldrich
Our study revealed that exposure of PC3 and MDA-MB-231 cells to Epigallocatechin gallate (EGCG), C-Gold nanoparticles (GNPs), or EGCG-gold nanoparticles (E-GNPs) induces apoptosis

Summary

Introduction

Cancer is a major public health problem worldwide [1]. There is a need to tackle cancer on multiple fronts, including the development of effective prevention and therapeutic strategies. One major issue with existing cancer chemotherapeutics is their high toxicity to healthy tissues at optimally effective doses, which limits their therapeutic potential [2,3]. Several dietary phytochemicals have emerged as molecules of choice due to their high antitumor properties and negligible toxicities [4]. Such agents suffer from poor solubility, stability, and cellular uptake; development of approaches is required to overcome these critical barriers [5]

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