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载 METase-培美曲塞的 PEG-PLGA 纳米粒的评价,其通过抗 CD133-scFV 修饰用于胃癌治疗。

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

机构信息

Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China

Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.

出版信息

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

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) 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.

摘要

聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒(NPs)经抗 CD133 和肿瘤靶向单链抗体片段(scFV)修饰后,可用于系统递 delivery 甲硫氨酸酶(METase)和培美曲塞治疗胃癌。成功制备了载甲硫氨酸酶-培美曲塞的 scFV-PEG-PLGA NPs(scFV-METase/pemetrexed-NPs),并对其结构特征和生物学功能进行了研究。功能 scFV-PEG-PLGA NPs 或 PEG-PLGA NPs 在 CD133+SGC7901 细胞中表现出低细胞毒性。scFV-METase/pemetrexed-NPs(scFv-M/P-NP)在抑制 CD133 阳性表达胃癌细胞的肿瘤生长(包括细胞生长和迁移能力)方面比 METase/pemetrexed-NPs(M/P-NP)更有效。此外,METase 增强了培美曲塞对胸苷酸合成酶(TS)合成和细胞凋亡的抑制作用。我们已经证明了 scFV 靶向 PEG-PLGA NPs 的应用是增强胃癌治疗效果的一种新的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e800/5789153/8a6fc84bcf3c/bsr-38-bsr20171001-g1.jpg

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