Active Tumor-Targeted co-Delivery of Epigallocatechin Gallate and Doxorubicin in Nanoparticles for Combination Gastric Cancer Therapy

Fwu Long Mi, Li Fang Wang, Pei Yi Chu, Shin Lei Peng, Chun Lung Feng, Ying Jing Lai, Jia Ni Li, Yu Hsin Lin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The clinical treatment of gastric cancer is hampered by the development of anticancer drug resistance as well as the unfavorable pharmacokinetics, nontarget toxicity, and inadequate intratumoral accumulation of current chemotherapies. The polyphenol epigallocatechin gallate in combination with doxorubicin exhibits synergistic inhibition P-glycoprotein efflux pump activity and cancer cell growth. This study evaluated a potential activated nanoparticle delivery system comprising a hyaluronic acid complex with polyethylene glycol-conjugated gelatin containing encapsulated epigallocatechin gallate and low-dose doxorubicin, which may facilitate targeted drug administration to gastric cancer cells. We confirmed successful delivery of bioactive combination drugs and internalization into gastric cancer cells through CD44 ligand recognition and ensuing inhibition of cell proliferation via caspase-induced apoptosis and G2/M phase cell cycle arrest. Furthermore, the targeted nanoparticles significantly suppressed gastric tumor activity and reduced both tumor and heart tissue inflammatory reaction in vivo compared to systemic combination treatment.

Original languageEnglish
Pages (from-to)2847-2859
Number of pages13
JournalACS Biomaterials Science and Engineering
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 13 2018

Fingerprint

Doxorubicin
Tumors
Cells
Nanoparticles
Hyaluronic acid
Glycoproteins
Pharmacokinetics
Chemotherapy
Cell proliferation
Cell growth
Polyphenols
P-Glycoprotein
Cell death
Drug Combinations
Hyaluronic Acid
Gelatin
Caspases
Pharmaceutical Preparations
Polyethylene glycols
Toxicity

Keywords

  • combination drugs
  • gastric cancer
  • nanoparticles
  • P-glycoprotein
  • synergistic

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

Cite this

Active Tumor-Targeted co-Delivery of Epigallocatechin Gallate and Doxorubicin in Nanoparticles for Combination Gastric Cancer Therapy. / Mi, Fwu Long; Wang, Li Fang; Chu, Pei Yi; Peng, Shin Lei; Feng, Chun Lung; Lai, Ying Jing; Li, Jia Ni; Lin, Yu Hsin.

In: ACS Biomaterials Science and Engineering, Vol. 4, No. 8, 13.08.2018, p. 2847-2859.

Research output: Contribution to journalArticle

Mi, Fwu Long ; Wang, Li Fang ; Chu, Pei Yi ; Peng, Shin Lei ; Feng, Chun Lung ; Lai, Ying Jing ; Li, Jia Ni ; Lin, Yu Hsin. / Active Tumor-Targeted co-Delivery of Epigallocatechin Gallate and Doxorubicin in Nanoparticles for Combination Gastric Cancer Therapy. In: ACS Biomaterials Science and Engineering. 2018 ; Vol. 4, No. 8. pp. 2847-2859.
@article{9b86270290f64513a4185c28b83c6a15,
title = "Active Tumor-Targeted co-Delivery of Epigallocatechin Gallate and Doxorubicin in Nanoparticles for Combination Gastric Cancer Therapy",
abstract = "The clinical treatment of gastric cancer is hampered by the development of anticancer drug resistance as well as the unfavorable pharmacokinetics, nontarget toxicity, and inadequate intratumoral accumulation of current chemotherapies. The polyphenol epigallocatechin gallate in combination with doxorubicin exhibits synergistic inhibition P-glycoprotein efflux pump activity and cancer cell growth. This study evaluated a potential activated nanoparticle delivery system comprising a hyaluronic acid complex with polyethylene glycol-conjugated gelatin containing encapsulated epigallocatechin gallate and low-dose doxorubicin, which may facilitate targeted drug administration to gastric cancer cells. We confirmed successful delivery of bioactive combination drugs and internalization into gastric cancer cells through CD44 ligand recognition and ensuing inhibition of cell proliferation via caspase-induced apoptosis and G2/M phase cell cycle arrest. Furthermore, the targeted nanoparticles significantly suppressed gastric tumor activity and reduced both tumor and heart tissue inflammatory reaction in vivo compared to systemic combination treatment.",
keywords = "combination drugs, gastric cancer, nanoparticles, P-glycoprotein, synergistic, combination drugs, gastric cancer, nanoparticles, P-glycoprotein, synergistic",
author = "Mi, {Fwu Long} and Wang, {Li Fang} and Chu, {Pei Yi} and Peng, {Shin Lei} and Feng, {Chun Lung} and Lai, {Ying Jing} and Li, {Jia Ni} and Lin, {Yu Hsin}",
year = "2018",
month = "8",
day = "13",
doi = "10.1021/acsbiomaterials.8b00242",
language = "English",
volume = "4",
pages = "2847--2859",
journal = "ACS Biomaterials Science and Engineering",
issn = "2373-9878",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Active Tumor-Targeted co-Delivery of Epigallocatechin Gallate and Doxorubicin in Nanoparticles for Combination Gastric Cancer Therapy

AU - Mi, Fwu Long

AU - Wang, Li Fang

AU - Chu, Pei Yi

AU - Peng, Shin Lei

AU - Feng, Chun Lung

AU - Lai, Ying Jing

AU - Li, Jia Ni

AU - Lin, Yu Hsin

PY - 2018/8/13

Y1 - 2018/8/13

N2 - The clinical treatment of gastric cancer is hampered by the development of anticancer drug resistance as well as the unfavorable pharmacokinetics, nontarget toxicity, and inadequate intratumoral accumulation of current chemotherapies. The polyphenol epigallocatechin gallate in combination with doxorubicin exhibits synergistic inhibition P-glycoprotein efflux pump activity and cancer cell growth. This study evaluated a potential activated nanoparticle delivery system comprising a hyaluronic acid complex with polyethylene glycol-conjugated gelatin containing encapsulated epigallocatechin gallate and low-dose doxorubicin, which may facilitate targeted drug administration to gastric cancer cells. We confirmed successful delivery of bioactive combination drugs and internalization into gastric cancer cells through CD44 ligand recognition and ensuing inhibition of cell proliferation via caspase-induced apoptosis and G2/M phase cell cycle arrest. Furthermore, the targeted nanoparticles significantly suppressed gastric tumor activity and reduced both tumor and heart tissue inflammatory reaction in vivo compared to systemic combination treatment.

AB - The clinical treatment of gastric cancer is hampered by the development of anticancer drug resistance as well as the unfavorable pharmacokinetics, nontarget toxicity, and inadequate intratumoral accumulation of current chemotherapies. The polyphenol epigallocatechin gallate in combination with doxorubicin exhibits synergistic inhibition P-glycoprotein efflux pump activity and cancer cell growth. This study evaluated a potential activated nanoparticle delivery system comprising a hyaluronic acid complex with polyethylene glycol-conjugated gelatin containing encapsulated epigallocatechin gallate and low-dose doxorubicin, which may facilitate targeted drug administration to gastric cancer cells. We confirmed successful delivery of bioactive combination drugs and internalization into gastric cancer cells through CD44 ligand recognition and ensuing inhibition of cell proliferation via caspase-induced apoptosis and G2/M phase cell cycle arrest. Furthermore, the targeted nanoparticles significantly suppressed gastric tumor activity and reduced both tumor and heart tissue inflammatory reaction in vivo compared to systemic combination treatment.

KW - combination drugs

KW - gastric cancer

KW - nanoparticles

KW - P-glycoprotein

KW - synergistic

KW - combination drugs

KW - gastric cancer

KW - nanoparticles

KW - P-glycoprotein

KW - synergistic

UR - http://www.scopus.com/inward/record.url?scp=85050337195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050337195&partnerID=8YFLogxK

U2 - 10.1021/acsbiomaterials.8b00242

DO - 10.1021/acsbiomaterials.8b00242

M3 - Article

VL - 4

SP - 2847

EP - 2859

JO - ACS Biomaterials Science and Engineering

JF - ACS Biomaterials Science and Engineering

SN - 2373-9878

IS - 8

ER -