The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs
The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs
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DOI：
10.1016/j.biomaterials.2011.11.032
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发表时间：
2012-02-01
期刊：
影响因子：
14
通讯作者：
Yang, Yi Yan
中科院分区：
文献类型：
--
作者：
Lee, Ashlynn L. Z.;Venkataraman, Shrinivas;Yang, Yi Yan
以单甲氧基聚乙二醇为原料，合成了一系列组成可控、多分散指数相对较低的可生物降解两亲性嵌段共聚物通过脂族环状碳酸酯单体-三亚甲基碳酸酯（TMC）或胆固醇2-（2-甲氧基苯基）-2-（3-甲氧基苯基）-1，3，4-三甲基胆固醇酯（mPEG-OH，5 kDa）的有机催化开环聚合，（5-甲基-2-氧代-1，3-二氧六环-5-羧酰氧基）乙基氨基甲酸酯在一个实施方案中，所述化合物包含两种单体（MTC-Chol）或两种单体（TMC和MTC-Chol）的共聚物：mPEG（113）-6-PTMC 67、mPEG（113）-b-P（MTC-Chol（11））和mPEG（113）-b-P（MTC-Chol（x）-co-TMCy）（x+y）。这些定义明确的聚合物被用来研究分子量和组成的聚合物的疏水嵌段在负载紫杉醇（PTX），一个非常疏水的抗癌药物与刚性结构和强烈的自缔合形成长纤维的倾向的作用。PTX负载胶束的制备通过简单的自组装没有超声或均质化程序。结果表明，在疏水嵌段中MTC-Chol和TMC两者的存在显著增加了PTX负载水平，并且由具有优化组成的聚合物（即mPEG（113）-b-P（MTC-Chol（11）-co-TMC 30））形成的胶束为纳米尺寸（36 nm），具有窄尺寸分布（PDI：0.07）和高PTX负载容量（15 wt.%）。用空白胶束体外处理人肝细胞肝癌HepG 2细胞显示，这些聚合物载体在2400 mg/L下无细胞毒性，细胞活力大于90%。重要的是，与游离PTX相比，负载艾德的胶束能够更有效地杀死癌细胞。此外，这些纳米载体还具有优异的动力学稳定性。来自非侵入性近红外荧光（NIRF）成像研究的结果表明，这些胶束允许有效的被动靶向，并且优选地在肿瘤组织中积累，而对健康器官的分布有限。(C)2011爱思唯尔有限公司保留所有权利。
A series of biodegradable amphiphilic block copolymers with controlled composition and relatively low polydispersity index were synthesized from monomethoxy polyethylene glycol (mPEG-OH, 5 kDa) via organocatalytic ring opening polymerization of aliphatic cyclic carbonate monomers - trimethylene carbonate (TMC) or cholesteryl 2-(5-methy1-2-oxo-1,3-dioxane-5-carboxyloyloxy)ethyl carbamate (MTC-Chol) or a copolymer of both the monomers (TMC and MTC-Chol): mPEG(113)-6-PTMC67, mPEG(113)-b-P(MTC-Chol(11)) and mPEG(113)-b-P(MTC-Chol(x)-co-TMCy)(x+y). These well-defined polymers were employed to study the role of molecular weight and composition of the hydrophobic block of the polymers in loading paclitaxel (PTX), an extremely hydrophobic anticancer drug with rigid structure and strong tendency of self-association to form long fibers. The PTX-loaded micelles were fabricated by simple self-assembly without sonication or homogenization procedures. The results demonstrated that the presence of both MTC-Chol and TMC in the hydrophobic block significantly increased PTX loading levels, and the micelles formed from the polymer with the optimized composition (i.e. mPEG(113)-b-P(MTC-Chol(11)-co-TMC30)) were in nanosize (36 nm) with narrow size distribution (PDI: 0.07) and high PTX loading capacity (15 wt.%). In vitro treatment of human liver hepatocellular carcinoma HepG2 cells with blank micelles showed that these polymeric carriers were non-cytotoxic with cell viability greater than 90% at 2400 mg/L Importantly, PTX-load ed micelles were able to kill cancer cells much more effectively compared to free PTX. In addition, these nanocarriers also possessed exceptional kinetic stability. The results from non-invasive near-infrared fluorescence (NIRF) imaging studies showed that these micelles allowed effective passive targeting, and were preferably accumulated in tumor tissue with limited distribution to healthy organs. (C) 2011 Elsevier Ltd. All rights reserved.