Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH.
Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH.
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DOI：
10.1002/smll.200701275
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发表时间：
2008-11
期刊：
影响因子：
13.3
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Kim, Dongin;Lee, Eun Seong;Oh, Kyung Taek;Gao, Zhong Gao;Bae, You Han
制备了一种优化的、ph敏感的叶酸偶联混合胶束体系，以对抗癌症的多药耐药（MDR）。胶束由聚组氨酸(His)-共苯丙氨酸(Phe) -聚乙二醇（PEG）和聚l -乳酸(PLLA)-b-聚乙二醇-叶酸组成。合成了不同组成的聚（His-co-Phe）成核、ph敏感的疏水块。研究了poly(His-co-Phe) （Mn= 5000 ~ 5500 Da）的组成依赖性pK值。胶束的pH敏感性大致由共聚物组成控制，通过混合PLLA(3K)-b-PEG(2K)-叶酸实现其对早期内体pH的微调，特别是在基本抗癌药物阿霉素（DOX）存在的情况下。为了证明胶束系统的有效性，我们对野生型（A2780）和抗dox卵巢癌细胞系（A2780/DOXR）进行了细胞活力、叶酸受体介导的内噬作用和内溶活性的体外实验。理化性质和体外结果,混合胶束体系组成的聚(His-co-Phe(摩尔%)16日)-b-PEG (80 wt %)和PLLA-b-PEG-folate (20 wt %)被选中目标早期endosomal博士DOX-loaded (ca。20 wt %)胶束有效杀死野生敏感和MDR癌症细胞系通过瞬时高剂量阿霉素的细胞溶质,带来活跃的内化,加速释放阿霉素endosomal引发的pH值,和一个中断endosomal pH。
An optimized, pH-sensitive mixed micelle system conjugated with folic acid was prepared to challenge multidrug resistance (MDR) in cancers. The micelles were composed of poly(histidine (His)-co-phenylalanine (Phe))-b-poly(ethylene glycol) (PEG) and poly(L-lactic acid) (PLLA)-b-PEG-folate. Core-forming, pH-sensitive hydrophobic blocks of poly(His-co-Phe) of varying composition were synthesized. The composition-dependent pK values of poly(His-co-Phe) (Mn=5,000−5,500 Da) were examined. The size and critical micelle concentration were evaluated as a function of pH. The pH sensitivity of the micelles was roughly controlled by the copolymer composition, and its fine tuning to early endosomal pH was achieved by blending PLLA(3K)-b-PEG(2K)-folate, especially in the presence of a basic anticancer drug, doxorubicin (DOX). To prove the efficacy of the micellar system, in vitro tests including cell viability, folate receptor-mediated endocytosis, and endosomolytic acitivity were conducted against both wild-type (A2780) and DOX-resistant ovarian carcinoma cell lines (A2780/DOXR). From the physicochemical properties and in vitro results, a mixed micelle system composed of poly(His-co-Phe (16 mole%))-b-PEG (80 wt%) and PLLA-b-PEG-folate (20 wt%) was selected to target early endosomal pH. DOX-loaded (ca. 20 wt%) micelles effectively killed both wild-type sensitive and MDR cancer cell lines through an instantaneous high dose of DOX in the cytosol, resulting from active internalization, accelerated DOX release triggered by endosomal pH, and a disruption of endosomal pH.
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影响因子：
4.8
作者：
Hu, Z;Jin, SK;Scotto, KW
通讯作者：
Scotto, KW
影响因子：
3.8
作者：
Liu, Z;Wu, XY;Bendayan, R
通讯作者：
Bendayan, R
影响因子：
3.7
作者：
Muller, RH;Ruhl, D;Mehnert, W
通讯作者：
Mehnert, W
DOI：
10.1016/s0927-7757(02)00389-8
发表时间：
2003-03-12
影响因子：
5.2
作者：
Han, SK;Na, K;Bae, YH
通讯作者：
Bae, YH
影响因子：
3.7
作者：
Mohajer, Ghazal;Lee, Eun Seong;Bae, You Han
通讯作者：
Bae, You Han