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Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice.

ABSTRACT: Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy.

SUBMITTER: Safwat MA

PROVIDER: S-EPMC7559993 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice.

Safwat Mohamed A MA Kandil Bothaina A BA Elblbesy Mohamed A MA Soliman Ghareb M GM Eleraky Nermin E NE

Pharmaceuticals (Basel, Switzerland) 20200918 9

Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the form ...[more]

PMID: 32961982

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Project description:Intimal macrophages play a critical role in atherosclerotic lesion initiation and progression by taking up oxidized low-density lipoprotein (oxLDL) and promoting inflammatory process. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a major type of oxidized phosphatidylcholines (PC) found on oxLDL, has a high binding affinity to the macrophage scavenger receptor CD36 and participates in CD36-mediated recognition and uptake of oxLDL by intimal macrophages. We successfully synthesized epigallocatechin gallate (EGCG)-loaded nanoparticles (Enano), which were composed of EGCG, PC, (+) alpha-tocopherol acetate, and surfactant. We also incorporated KOdiA-PC on the surface of Enano to make ligand-coated Enano (L-Enano) to target intimal macrophages. The objectives of this study were to determine the anti-atherogenic effects of Enano and L-Enano in LDL receptor null (LDLr-/-) mice. Our in vitro data demonstrated that L-Enano had a higher binding affinity to mouse peritoneal macrophages than Enano. This high binding affinity was diminished by CD36 antibodies or knockdown of the CD36 receptor in mouse peritoneal macrophages, confirming the specific binding of L-Enano to the macrophage CD36 receptor. LDLr-/- mice were randomly divided to six groups and received weekly tail vein injection with PBS, EGCG, void nanoparticles (Vnano), Enano, ligand-coated Vnano (L-Vnano), or L-Enano once per week for 22?weeks. The dose of EGCG was 25?mg per kg body weight. L-Enano at 20??g/mL significantly decreased production of monocyte chemoattractant protein-1, tumor necrosis factor alpha, and interleukin-6 from mouse macrophages, while having no effect on their plasma levels compared to the PBS control. There were no significant differences in blood lipid profiles among six treatment groups. Mice treated with L-Enano also had significantly smaller lesion surface areas on aortic arches compared to the PBS control. Liver EGCG content was decreased by treatments in the order of EGCG>Enano>L-Enano. Native EGCG had inhibitory effects on liver and body fat accumulation. This molecular target approach signals an important step towards inhibiting atherosclerosis development via targeted delivery of bioactive compounds to intimal macrophages.

Dataset Information

Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice.

Publications

Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice.

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