In vivo evaluation of doxorubicin-loaded polymeric micelles targeting folate receptors and early endosomal pH in drug-resistant ovarian cancer.
In vivo evaluation of doxorubicin-loaded polymeric micelles targeting folate receptors and early endosomal pH in drug-resistant ovarian cancer.
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DOI：
10.1021/mp900021q
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发表时间：
2009-09
影响因子：
4.9
通讯作者：
Bae YH
中科院分区：
文献类型：
--
作者：
Kim D;Gao ZG;Lee ES;Bae YH
第二代pH敏感胶束由聚(L-组氨酸-co-L-苯丙氨酸(16mol%))(相对分子质量：5K)-b-聚乙二醇(相对分子质量：2K)和聚(L-乳酸)(相对分子质量：3K)-b-聚乙二醇(相对分子质量：2K)-叶酸(80/20wt/wt%)组成，通过叶酸受体和早期膜pH靶向性(pH~6.0)的物理化学和体外实验进行了优化。本研究通过体内实验评价了阿霉素胶束(DOX载药量为20wt%)的治疗效果。采用多药耐药(MDR)卵巢肿瘤移植模型。采用皮肤折叠背侧窗腔模型显示静脉注射后最初1小时的渗出和药物滞留。注射。随后进行了非侵入性成像，在第一个小时后提供了药物在肿瘤中积聚的证据。生物分布研究进一步支持药物载体的长循环、肿瘤选择性蓄积和细胞内给药。全面的肿瘤生长抑制实验检测了pH敏感胶束的集体效果。该胶束制剂通过三次静脉注射有效地抑制了现有的小鼠多药耐药肿瘤的生长至少50天。每隔3天注射一次，剂量为10 mg DOX/kg。用试验胶束制剂处理的动物的体重随着实验时间的推移逐渐增加，而不是减少。胶束配方优于第一代胶束，第一代胶束针对的是pH 6.8和叶酸受体。
The second generation of pH-sensitive micelles composed of poly(L-histidine-co-L-phenlyalanine (16 mol%))(MW: 5K)-b-PEG(MW: 2K) and poly(L-lactic acid)(MW: 3K)-b-PEG(MW: 2K)-folate (80/20 wt/wt%) was previously optimized by physicochemical and in vitro tests for both folate receptor and early endosomal pH targeting (pH ~6.0). In this study, the therapeutic efficacy of the doxorubicin (DOX)-loaded micelles (DOX loading content: 20wt %) was evaluated using in vivo tests. Multidrug-resistant (MDR) ovarian tumor-xenografted mouse models were employed. The skin-fold dorsal window chamber model was applied for visualization of extravasation and drug retention for the initial one hour after i.v. injection. Non-invasive imaging followed, providing evidence of drug accumulation in the tumor after the first hour. The biodistribution study further supported the long circulation of the drug carrier, tumor-selective accumulation and intracellular drug delivery. Comprehensive tumor growth inhibition experiments examined the collective efficacy of the pH-sensitive micelles. The micelle formulation effectively suppressed the growth of existing MDR tumors in mice for at least 50 days by three i.v. injections at a 3-day interval at a dose of 10 mg DOX/kg. The body weight of the animals treated with the test micelle formulation gradually increased over the experimental time period, rather than decreasing. The micelle formulation was superior to its first generation, which targeted pH 6.8 and folate receptor.
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影响因子：
4.8
作者：
Carneiro, FA;Stauffer, F;Da Poian, AT
通讯作者：
Da Poian, AT
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
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：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K
影响因子：
4.7
作者：
Gopin, Anna;Ebner, Sharon;Shabat, Doron
通讯作者：
Shabat, Doron