The effect of surface functionalization of PLGA nanoparticles by heparin- or chitosan-conjugated Pluronic on tumor targeting
The effect of surface functionalization of PLGA nanoparticles by heparin- or chitosan-conjugated Pluronic on tumor targeting
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DOI：
10.1016/j.jconrel.2010.01.017
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发表时间：
2010-05-10
影响因子：
10.8
通讯作者：
Kwon, Ick Chan
中科院分区：
文献类型：
--
作者：
Chung, Yong-Il;Kim, Jong Chul;Kwon, Ick Chan
采用肝素-或壳聚糖- pluronic偶联物包被的聚丙交酯-羟基乙酸酯（PLGA）纳米颗粒，可以提高裸PLGA纳米颗粒相对较低的肿瘤靶向效率。制备的纳米颗粒的尺寸范围为100-150 nm，功能片段（肝素或壳聚糖）的表面暴露分别通过负或正增加的zeta电位值来证实。正常细胞和肿瘤细胞的活力测试显示，纳米颗粒的细胞毒性很小。尽管在血清环境中表面电荷发生变化，但稳定的表面涂层的大小分布曲线没有变化，这表明它有效地提供了所需的功能化表面，明显增强了纳米颗粒对肝素和壳聚糖功能化的体外细胞摄取。在SCC7荷瘤胸腺小鼠体内进行的肿瘤模型研究表明，表面功能化具有有限但积极的作用，壳聚糖功能化更有效。壳聚糖功能化的PLGA纳米颗粒在肿瘤中的蓄积量比裸体Pluronic包被的PLGA纳米颗粒高2.4倍，在肝脏中的蓄积量比对照组低。肝素功能化组的平均值是对照组的2.2倍，但肝脏累积量与对照组相似。因此，壳聚糖或肝素偶联Pluronic的表面功能化可能是一种有效的疏水纳米颗粒系统，旨在增强肿瘤成像和治疗。(C) 2010 Elsevier B.V.版权所有
The poly (lactide-co-glycolide) (PLGA)-based nanoparticles, coated by the heparin- or chitosan-Pluronic conjugate, were used to improve a relatively low tumor-targeting efficiency of the bare PLGA nanoparticles. The prepared nanoparticles were in the size range of 100-150 nm, and the surface exposure of the functional moiety (heparin or chitosan) was confirmed by negatively or positively increased zeta potential values, respectively. The viability tests for both normal and tumor cells displayed minimal cytotoxicity of the nanoparticles. The stable surface coating, which was evident from no change in the size distribution profiles in spite of the surface charge changes in serum environment, effectively provided the desired functionalized surface that clearly enhanced the in vitro cellular uptake of the nanoparticles for both heparin and chitosan functionalization. The in vivo tumor model study, which was carried out in SCC7 tumor-bearing athymic mice, demonstrated that there was a limited, but positive effect of surface functionalization, more effective for chitosan functionalization. The accumulation of chitosan-functionalized PLGA nanoparticles in tumor was 2.4 folds higher than that of the control, PLGA nanoparticles coated with bare Pluronic, and the accumulation in liver was lower than the control. In the case of heparin functionalization, the mean value was 2.2 folds higher than that of the control, but the accumulation in liver was similar to that of the control. Therefore, the surface-functionalization by the chitosan- or heparin-conjugated Pluronic may be an effective approach for the hydrophobic nanoparticle systems aiming for the enhanced tumor imaging and therapy. (C) 2010 Elsevier B.V. All rights reserved.