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已发表论文
曲妥珠单抗和 Fab′ 片段修饰的姜黄素 PEG-PLGA 纳米颗粒: 制备及体内体外评估
Authors Duan D, Wang A, Ni L, Zhang L, Yan X, Jiang Y, Mu H, Wu Z, Sun K, Li Y
Received 11 October 2017
Accepted for publication 24 January 2018
Published 22 March 2018 Volume 2018:13 Pages 1831—1840
DOI https://doi.org/10.2147/IJN.S153795
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 4
Editor who approved publication: Dr Linlin Sun
Introduction: Nanoparticles
(NPs) modified with bio-ligands represent a promising strategy for active
targeted drug delivery to tumour. However, many targeted ligands, such as
trastuzumab (TMAB), have high molecular weight, limiting their application for
targeting. In this study, we prepared Fab’ (antigen-binding fragments cut from
TMAB)-modified NPs (Fab'-NPs) with curcumin (Cur) as a model drug for more
effective targeting of human epidermal growth factor receptor 2
(HER2/ErbB2/Neu), which is overexpressed on breast cancer cells.
Material and methods: The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS).
Results: The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs.
Conclusion: Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery.
Keywords: trastuzumab-modified curcumin nanoparticles, Fab'-modified curcumin nanoparticles, pharmacokinetics, biodistribution, tumour targeting, breast cancer
Material and methods: The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS).
Results: The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs.
Conclusion: Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery.
Keywords: trastuzumab-modified curcumin nanoparticles, Fab'-modified curcumin nanoparticles, pharmacokinetics, biodistribution, tumour targeting, breast cancer
