Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles
Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles
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DOI：
10.1016/j.jconrel.2007.04.009
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发表时间：
2007-10-08
影响因子：
10.8
通讯作者：
Kwon, Ick Chan
中科院分区：
文献类型：
--
作者：
Park, Kyeongsoon;Kim, Jong-Ho;Kwon, Ick Chan
为了提高聚合物纳米粒的体内肿瘤靶向性，以胆甾烷酸为修饰剂，对不同分子量（GC-20 kDa、GC-100 kDa和GC-250 kDa）的衍生物进行修饰，得到两亲性的乙二醇壳聚糖-胆甾烷酸偶联物，通过自组装形成乙二醇壳聚糖纳米粒（GC-20 kDa-NP、GC-100 kDa-NP和GC-250 kDa-NP）。所有三种乙二醇壳聚糖纳米颗粒的物理化学性质，包括胆烷酸取代度，表面电荷，粒径和体外稳定性，是相似的，无论分子量。使用近红外（NIR）荧光团Cy5.5标记的乙二醇壳聚糖纳米颗粒在SCC 7荷瘤小鼠中的体内组织分布、时间依赖性排泄和肿瘤蓄积进行了监测。乙二醇壳聚糖纳米颗粒显示出延长的血液循环时间，减少体内的时间依赖性排泄，并随着聚合物分子量的增加而增加肿瘤蓄积。这些结果共同表明，高分子量乙二醇壳聚糖纳米颗粒在血液循环中停留的时间更长，导致肿瘤部位的积累增加。因此，我们提出，基于血液循环时间的药代动力学改善，高分子量乙二醇壳聚糖纳米颗粒增强的肿瘤靶向与更好的体内稳定性有关。(c)2007 Elsevier B. V.保留所有权利。
To improve the in vivo tumor targeting characteristics of polymeric nanoparticles, three glycol chitosan (GC-20 kDa, GC-100 kDa, and GC-250 kDa) derivatives with different molecular weights were modified with cholanic acid at the same molar ratio, The resulting amphiphilic glycol chitosan-cholanic acid conjugates self-assembled to form glycol chitosan nanoparticles (GC-20 kDa-NP, GC-100 kDa-NP, and GC-250 kDa-NP) under aqueous conditions. The physicochemical properties of all three glycol chitosan nanoparticles, including degree of substitution with cholanic acid, surface charge, particle size and in vitro stability, were similar regardless of molecular weight. In vivo tissue distribution, time-dependent excretion, and tumor accumulation of glycol chitosan nanoparticles labeled with the near-infrared (NIR) fluorophore, Cy5.5, were monitored in SCC7 tumor-bearing mice, using NIR fluorescence imaging systems. Glycol chitosan nanoparticles displayed prolonged blood circulation time, decreased time-dependent excretion from the body, and elevated tumor accumulation with increasing polymer molecular weight. The results collectively suggest that high molecular weight glycol chitosan nanoparticles remain for longer periods in the blood circulation, leading to increased accumulation at the tumor site. Accordingly, we propose that enhanced tumor targeting by high molecular weight glycol chitosan nanoparticles is related to better in vivo stability, based on a pharmacokinetic improvement in blood circulation time. (c) 2007 Elsevier B.V. All rights reserved.