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本文引用的文献

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Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery.通过pH敏感腙键与阿霉素共轭的两亲性多臂嵌段共聚物用于肿瘤靶向给药。
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Nanocarriers as an emerging platform for cancer therapy.纳米载体作为一种新兴的癌症治疗平台。
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Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid.叶酸靶向的聚乙二醇化吉西他滨前药的抗肿瘤活性
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Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases.基于叶酸的受体靶向用于癌症和炎症性疾病成像与治疗的发现与开发。
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The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform.基于纳米颗粒的多价靶向药物递送平台的结合亲和力。
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HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction between a folate-dendrimer conjugate and folate binding protein.功能化聚（酰胺胺）树枝状大分子的高效液相色谱分析以及叶酸 - 树枝状大分子共轭物与叶酸结合蛋白之间的相互作用。
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PAMAM dendrimer-based multifunctional conjugate for cancer therapy: synthesis, characterization, and functionality.基于聚酰胺-胺（PAMAM）树枝状大分子的癌症治疗多功能共轭物：合成、表征及功能
Biomacromolecules. 2006 Feb;7(2):572-9. doi: 10.1021/bm0506142.
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Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy.用于癌症治疗的基于聚（酰胺胺）树枝状大分子的多功能工程纳米器件。
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Folate receptor-mediated drug targeting: from therapeutics to diagnostics.叶酸受体介导的药物靶向：从治疗到诊断
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Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer.纳米颗粒靶向抗癌药物可改善人类上皮癌动物模型中的治疗反应。
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靶向树枝状抗癌前药：一种甲氨蝶呤-叶酸-聚（酰胺胺）共轭物及一种新型、快速的“一锅法”合成方法。

Targeted dendrimeric anticancer prodrug: a methotrexate-folic acid-poly(amidoamine) conjugate and a novel, rapid, "one pot" synthetic approach.

作者信息

Zhang Yuehua, Thomas Thommey P, Desai Ankur, Zong Hong, Leroueil Pascale R, Majoros Istvan J, Baker James R

机构信息

Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109.

出版信息

Bioconjug Chem. 2010 Mar 17;21(3):489-95. doi: 10.1021/bc9003958. Epub 2010 Feb 3.

DOI:10.1021/bc9003958
PMID:20128612
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2892195/
Abstract

A targeted dendrimeric anticancer prodrug, a conjugate of generation 5 (G5) polyamidoamine (PAMAM) dendrimer, folic acid (FA), and methotrexate (MTX), has been successfully synthesized by using a novel "one pot" approach which is simple, reproducible, and feasible for large-scale synthesis. All dendrimer products have been characterized by (1)H NMR, MALDI-TOF, GPC, and HPLC. With this new method, the ratio of FA versus MTX attached to the dendrimer can be easily tuned to achieve the desired therapeutic effect. A new analytical approach for calculating the numbers of FA and MTX attached to the dendrimer has been established. In vitro studies performed on FA receptor-expressing KB cells show that the new conjugate has a similar affinity and cytotoxic potency to G5-FA-MTX synthesized using the traditional multiple-step approach.

摘要

一种靶向树枝状抗癌前药，即第5代（G5）聚酰胺-胺（PAMAM）树枝状大分子、叶酸（FA）和甲氨蝶呤（MTX）的共轭物，已通过一种新颖的“一锅法”成功合成，该方法简单、可重复且适用于大规模合成。所有树枝状大分子产物均已通过¹H NMR、基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）、凝胶渗透色谱（GPC）和高效液相色谱（HPLC）进行了表征。采用这种新方法，可以轻松调节连接到树枝状大分子上的FA与MTX的比例，以实现所需的治疗效果。已建立了一种计算连接到树枝状大分子上的FA和MTX数量的新分析方法。在表达FA受体的KB细胞上进行的体外研究表明，这种新的共轭物与使用传统多步方法合成的G5-FA-MTX具有相似的亲和力和细胞毒性效力。