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The folate receptor as a rational therapeutic target for personalized cancer treatment.叶酸受体作为一种合理的治疗靶点,用于癌症的个体化治疗。
Drug Resist Updat. 2014 Oct-Dec;17(4-6):89-95. doi: 10.1016/j.drup.2014.10.002. Epub 2014 Oct 8.
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Trastuzumab-conjugated liposome-coated fluorescent magnetic nanoparticles to target breast cancer.曲妥珠单抗偶联脂质体包被的荧光磁性纳米颗粒用于靶向乳腺癌。
Korean J Radiol. 2014 Jul-Aug;15(4):411-22. doi: 10.3348/kjr.2014.15.4.411. Epub 2014 Jul 9.
3
pH-sensitive polymeric nanoparticles for tumor-targeting doxorubicin delivery: concept and recent advances.用于肿瘤靶向阿霉素递送的 pH 敏感聚合物纳米粒:概念和最新进展。
Nanomedicine (Lond). 2014 Mar;9(3):487-99. doi: 10.2217/nnm.13.212.
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Hyperthermia-mediated local drug delivery by a bubble-generating liposomal system for tumor-specific chemotherapy.超声空化介导载药脂质体系统实现肿瘤热化疗
ACS Nano. 2014 May 27;8(5):5105-15. doi: 10.1021/nn501162x. Epub 2014 Apr 21.
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The anti-tumoral efficacy of a docetaxel-loaded liposomal drug delivery system modified with transferrin for ovarian cancer.一种用转铁蛋白修饰的载多西他赛脂质体药物递送系统对卵巢癌的抗肿瘤疗效。
Drug Res (Stuttg). 2014 Apr;64(4):195-202. doi: 10.1055/s-0033-1355335. Epub 2013 Oct 23.
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J Microbiol Biotechnol. 2012 Dec;22(12):1782-9. doi: 10.4014/jmb.1208.08031.
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In vitro and in vivo antitumor activity of a novel pH-activated polymeric drug delivery system for doxorubicin.新型 pH 激活型多柔比星聚合物药物递送系统的体内外抗肿瘤活性。
PLoS One. 2012;7(9):e44116. doi: 10.1371/journal.pone.0044116. Epub 2012 Sep 24.
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Emulsion forming drug delivery system for lipophilic drugs.用于亲脂性药物的乳液形成给药系统。
Acta Pol Pharm. 2012 Mar-Apr;69(2):179-91.
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Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile.一种具有差异化药代动力学特征的 PSMA 靶向多西他赛纳米颗粒的临床前开发和临床转化。
Sci Transl Med. 2012 Apr 4;4(128):128ra39. doi: 10.1126/scitranslmed.3003651.
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Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles.RGD修饰的聚乳酸-羟基乙酸共聚物纳米颗粒对肿瘤内皮细胞的靶向作用
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用于阿霉素靶向递送的基于生物聚合物的纳米系统。

Biopolymer based nanosystem for doxorubicin targeted delivery.

作者信息

Csikós Zsuzsanna, Kerekes Krisztina, Fazekas Erika, Kun Sándor, Borbély János

机构信息

BBS Nanotechnology Ltd. Böszörményi 212., H-4032 Debrecen, Hungary.

BBS Nanotechnology Ltd.Böszörményi 212., H-4032 Debrecen, Hungary; Department of Radiology, Faculty of Medicine, University of DebrecenNagyerdei krt. 94., H-4032 Debrecen, Hungary.

出版信息

Am J Cancer Res. 2017 Mar 1;7(3):715-726. eCollection 2017.

PMID:28401023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5385654/
Abstract

This study describes formation of an actively and passively targeted, water-soluble drug delivery system (DDS) which contains doxorubicin (DOX). The system comprises two biocompatible and biodegradable polymers: poly-γ-glutamic acid (PGA) and chitosan (CH). Self-assembly of these biopolymers in aqueous medium results stable nanoparticles (NPs) with a hydrodynamic size of 80-150 nm and slightly negative surface charge. Folic acid (FA) was used as targeting agent bonded to the polyanion (PA) and also to the surface of the NPs. The NP's physical stability, active targeting effect, cellular toxicity, release profile and anti-tumor efficacy were investigated. It was found that the targeted, self-assembled nanoparticles are stable at 4°C for several months, cause better toxicity effect on folate receptor (FR) positive cell lines than the doxorubicin or the non-targeted nanosystem and based on its release profile it is expected, that the nanosystem will remain stable during the circulation in the body. Pharmacodynamic studies demonstrated that the DOX-loaded nanoparticles can deliver greater tumor growth inhibition than the free drug molecules and the liposomal compound, with less general toxicity. It was observed that the overall survival is the main benefit of the biopolymer based drug delivery system.

摘要

本研究描述了一种含有阿霉素(DOX)的主动和被动靶向水溶性药物递送系统(DDS)的形成。该系统由两种生物相容性和可生物降解的聚合物组成:聚γ-谷氨酸(PGA)和壳聚糖(CH)。这些生物聚合物在水性介质中的自组装产生了稳定的纳米颗粒(NPs),其流体动力学尺寸为80 - 150 nm,表面电荷略带负电。叶酸(FA)用作靶向剂,与聚阴离子(PA)以及NPs的表面相连。研究了NP的物理稳定性、主动靶向效果、细胞毒性、释放曲线和抗肿瘤功效。结果发现,靶向自组装纳米颗粒在4°C下可稳定存在数月,对叶酸受体(FR)阳性细胞系的毒性作用比阿霉素或非靶向纳米系统更好,并且基于其释放曲线,预计该纳米系统在体内循环过程中会保持稳定。药效学研究表明,负载DOX的纳米颗粒比游离药物分子和脂质体化合物能更有效地抑制肿瘤生长,且全身毒性更小。观察到基于生物聚合物的药物递送系统的主要益处是提高总体生存率。