Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, South Korea.
J Control Release. 2010 May 10;143(3):374-82. doi: 10.1016/j.jconrel.2010.01.017. Epub 2010 Jan 25.
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 100-150nm, 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.
基于聚（乳酸-共-乙醇酸）（PLGA）的纳米粒子，通过肝素或壳聚糖-泊洛沙姆缀合物进行涂层，用于提高裸 PLGA 纳米粒子相对较低的肿瘤靶向效率。所制备的纳米粒子的粒径范围为 100-150nm，并且通过分别负或正增加的 ζ 电位值，确认了功能部分（肝素或壳聚糖）的表面暴露。对于正常细胞和肿瘤细胞的活力测试均显示纳米粒子具有最小的细胞毒性。稳定的表面涂层，尽管在血清环境中表面电荷发生变化，但从粒径分布谱不变可以明显看出，这有效地提供了所需的功能化表面，明显增强了肝素和壳聚糖功能化的体外细胞摄取。在 SCC7 荷瘤裸鼠进行的体内肿瘤模型研究表明，表面功能化具有有限但积极的作用，壳聚糖功能化更为有效。壳聚糖功能化 PLGA 纳米粒子在肿瘤中的积累是对照（裸泊洛沙姆涂层的 PLGA 纳米粒子）的 2.4 倍，在肝脏中的积累低于对照。在肝素功能化的情况下，平均值比对照高 2.2 倍，但在肝脏中的积累与对照相似。因此，通过壳聚糖或肝素缀合的泊洛沙姆进行表面功能化可能是针对增强肿瘤成像和治疗的疏水性纳米粒子系统的有效方法。
