Evaluation of METase-pemetrexed-loaded PEG-PLGA nanoparticles modified with anti-CD133-scFV for treatment of gastric carcinoma

Lin Xin; Hou-Ting Zhang; Wei-Feng Yang; Yi-Fan Li; Chuan Liu

doi:10.1042/BSR20171001

Evaluation of METase-pemetrexed-loaded PEG-PLGA nanoparticles modified with anti-CD133-scFV for treatment of gastric carcinoma

Biosci Rep. 2018 Jan 30;38(1):BSR20171001. doi: 10.1042/BSR20171001. Print 2018 Feb 28.

Authors

Lin Xin¹, Hou-Ting Zhang², Wei-Feng Yang², Yi-Fan Li², Chuan Liu²

Affiliations

¹ Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China Lin_Xin1234@163.com.
² Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.

Abstract

PEG-PLGA nanoparticles (NPs) modified with anti-CD133 and tumor-targeting single-chain antibody fragment (scFV-NPs) for systemic delivery of methioninase (METase) and pemetrexed for gastric carcinoma were successfully formulated. The structure characterization and biological functions of METase-pemetrexed-loaded scFV-PEG-PLGA NPs (scFV-METase/pemetrexed-NPs) in vitro were investigated. Functional scFV-PEG-PLGA NPs or PEG-PLGA NPs present low cell cytoxicity in CD133+ SGC7901 cells. scFV-METase/pemetrexed-NPs (scFv-M/P-NP) was more effective in inhibiting tumor growth (including cell growth and migration ability) in CD133 positive expressed gastric cancer cells than METase/pemetrexed-NPs (M/P-NP). Moreover, METase enhanced the inhibitory effect of pemetrexed on thymidylate synthase (TS) synthesis and cell apoptosis. We have demonstrated the application of scFV-targeted PEG-PLGA NPs as a new potential strategy to enhance treatment benefits for gastric carcinoma.

Keywords: CD133; PEG-PLGA nanoparticles; gastric carcinoma; methioninase; pemetrexed; scFV.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AC133 Antigen / administration & dosage
AC133 Antigen / chemistry
Carbon-Sulfur Lyases / administration & dosage
Carbon-Sulfur Lyases / chemistry
Cell Line, Tumor
Cell Survival / drug effects
Drug Carriers / administration & dosage
Drug Carriers / chemistry
Humans
Lactic Acid / administration & dosage*
Lactic Acid / chemistry
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Pemetrexed / chemistry
Polyesters / administration & dosage
Polyesters / chemistry
Polyethylene Glycols / administration & dosage
Polyethylene Glycols / chemistry
Polyglycolic Acid / administration & dosage*
Polyglycolic Acid / chemistry
Polylactic Acid-Polyglycolic Acid Copolymer
Single-Chain Antibodies / administration & dosage*
Single-Chain Antibodies / chemistry
Stomach Neoplasms / drug therapy*
Stomach Neoplasms / pathology

Substances

AC133 Antigen
Drug Carriers
Polyesters
Single-Chain Antibodies
polyethylene glycol-poly(lactide-co-glycolide)
Pemetrexed
Polylactic Acid-Polyglycolic Acid Copolymer
Polyglycolic Acid
Lactic Acid
Polyethylene Glycols
Carbon-Sulfur Lyases
PEG-methioninase