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

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.