Evaluation of METase-pemetrexed-loaded PEG–PLGA nanoparticles modified with anti-CD133–scFV for treatment of gastric carcinoma
Evaluation of METase-pemetrexed-loaded PEG–PLGA nanoparticles modified with anti-CD133–scFV for treatment of gastric carcinoma
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DOI：
10.1042/bsr20171001
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发表时间：
2017-12
影响因子：
4
通讯作者：
L. Xin;Hou-Ting Zhang;Wei-feng Yang;Yi-Fan Li;Chuan Liu
中科院分区：
文献类型：
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作者：
L. Xin;Hou-Ting Zhang;Wei-feng Yang;Yi-Fan Li;Chuan Liu
成功地制备了抗CD133修饰的聚乙二醇单抗纳米粒(NPs)和肿瘤靶向单链抗体片段(scFv-NPs)，用于蛋氨酸酶(METase)和培美曲塞的全身给药。研究了METase-培美曲塞单链抗体/聚乙二醇单抗纳米粒(scFv-METase/派美曲塞-NPs)的结构表征和体外生物学功能。在CD133+SGC7901细胞中，功能性ScFv-PEG-PLGA纳米粒或PEG-PLGA纳米粒具有较低的细胞毒性。在CD133阳性表达的胃癌细胞中，ScFv-METase/培美曲塞-NPs(scFv-M/P-NP)对肿瘤生长(包括细胞生长和迁移能力)的抑制作用比METase/培美曲塞-NPs(M/P-NP)更有效。此外，METase还增强了培美曲塞对胸苷合成酶(TS)合成和细胞凋亡的抑制作用。我们已经展示了单链抗体靶向的聚乙二醇聚乳酸纳米粒作为一种新的潜在策略的应用，以提高胃癌的治疗效益。
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.