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.