Enhanced anti-colon cancer efficacy of 5-fluorouracil by epigallocatechin-3- gallate co-loaded in wheat germ agglutinin-conjugated nanoparticles.

Abstract

Colon adenocarcinoma is the third most common cause of cancer-related deaths worldwide owing to its aggressive nature. Here, we developed a novel oral drug delivery system (DDS) that comprised active targeted nanoparticles made from gelatin and chitosan (non-toxic polymers). The nanoparticles were fabricated using a complex coacervation method, which was accompanied by conjugation of wheat germ agglutinin (WGA) onto their surface by glutaraldehyde cross-linking. Specifically, we integrated 5-fluorouracil (5-FU), the first-line treatment agent against colon cancer, and (-)-epigallocatechin-3-gallate (EGCG), which inhibits tumor growth via anti-angiogenesis and apoptosis-inducing effects, into the nanoparticles, named WGA-EF-NP. The 5-FU and EGCG co-loaded nanoparticles showed sustained drug release, enhanced cellular uptake, and longer circulation time. WGA-EF-NP exhibited superior anti-tumor activity and pro-apoptotic efficacy compared to the drugs and nanoparticles without WGA decoration owing to better bioavailability and longer circulation time in vivo. Thus, WGA-EF-NP shows promise as a DDS for enhanced efficacy against colon cancer.

• Authors: Ruoning Wang, Jinyu Huang, Jian Chen, Mengmeng Yang, Honglan Wang, Hongzhi Qiao, Zhipeng Chen, Lihong Hu, Liuqing Di, Junsong Li
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 21 Pg. 102068 (10 2019) ISSN: 1549-9642 [Electronic] United States
• PMID: 31374249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Nanoconjugates
• Wheat Germ Agglutinins
• Catechin
• epigallocatechin gallate
• Fluorouracil

Topics

• Animals
• Apoptosis (drug effects)
• Catechin (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Colonic Neoplasms (blood supply, drug therapy, metabolism, pathology)
• Fluorouracil (chemistry, pharmacokinetics, pharmacology)
• HT29 Cells
• Humans
• Mice
• Nanoconjugates (chemistry, therapeutic use)
• Neovascularization, Pathologic (drug therapy, metabolism, pathology)
• Wheat Germ Agglutinins (chemistry, pharmacokinetics, pharmacology)
• Xenograft Model Antitumor Assays