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人绒毛膜促性腺激素多肽纳米颗粒给药系统提高甲氨蝶呤在体外妊娠滋养细胞肿瘤中的疗效。

Human Chorionic Gonadotropin Polypeptide Nanoparticle Drug Delivery System Improves Methotrexate Efficacy in Gestational Trophoblastic Neoplasia in vitro.

作者信息

Cong Qing, Lin Ling, Qi Biao, Xu Congjian, Zhang Xiaoyan

机构信息

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.

Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Feb 18;13:1699-1708. doi: 10.2147/CMAR.S279831. eCollection 2021.

Abstract

PURPOSE

To alleviate the sufferings of the chemotherapy patients, we developed a novel active targeted therapeutic system and showed its potential as a promising drug delivery strategy.

METHODS

We utilized the human chorionic gonadotropin (HCG) ligand-receptor mediation to make an actively targeted drug delivery system with optimal HCG polypeptide fragment as target head base, polyethylene glycol-polylactic acid copolymers as nanometer materials to load chemotherapy drug methotrexate (MTX), to highly selectively deliver MTX into choriocarcinoma lesions, and to investigate the efficacy, targeting and tolerability of the complex in vitro experiments.

RESULTS

Our data show that choriocarcinoma cell lines JEG-3 and JAR exhibited high expression levels of HCG receptor, peptide HCGβ81-95 specifically bonded to HCG receptor-positive cells and HCG81-NP efficiently delivered MTX to choriocarcinoma cells. HCG81-NP-MTX inhibited cell proliferation and reduced G/G to S phase transition in JEG-3 and JAR cells.

CONCLUSION

We designed an active targeting therapy system of choriocarcinoma, significantly improved chemotherapy efficacy in vitro, and provided a theoretical basis for the treatment of malignant trophoblastic tumors.

摘要

目的

为减轻化疗患者的痛苦,我们研发了一种新型主动靶向治疗系统,并展示了其作为一种有前景的药物递送策略的潜力。

方法

我们利用人绒毛膜促性腺激素(HCG)配体-受体介导作用,构建了一种主动靶向药物递送系统,以最佳的HCG多肽片段为靶向头部基团,聚乙二醇-聚乳酸共聚物为纳米材料来负载化疗药物甲氨蝶呤(MTX),将MTX高度选择性地递送至绒毛膜癌病灶,并在体外实验中研究该复合物的疗效、靶向性和耐受性。

结果

我们的数据表明,绒毛膜癌细胞系JEG-3和JAR表现出高表达水平的HCG受体,肽段HCGβ81-95特异性结合至HCG受体阳性细胞,且HCG81-NP能有效地将MTX递送至绒毛膜癌细胞。HCG81-NP-MTX抑制了JEG-3和JAR细胞的增殖,并减少了G/G期至S期的转变。

结论

我们设计了一种绒毛膜癌主动靶向治疗系统,显著提高了体外化疗疗效,为恶性滋养细胞肿瘤的治疗提供了理论依据。

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