Department of Materials Science and Engineering and Department of Nanobio Materials and Electronics, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Korea.
J Control Release. 2010 Oct 1;147(1):109-17. doi: 10.1016/j.jconrel.2010.06.010. Epub 2010 Jun 19.
Pluronic-based nano-carriers including bare forms that were composed of Pluronic F 68(NC(PF 68)) or Pluronic F 127(NC(PF 127)), and chitosan-conjugated forms (Chito-NC(PF 68) or Chito-NC(PF 127)) were prepared by photo-polymerizing two kinds of diacrylated Pluronic (F 68 and F 127) and acrylated chitosan to investigate the effect of chitosan conjugation and their physicochemical characteristics (size and hydrophilicity) of Pluronic-based nano-carriers on the tumor targeting efficiency. All of the nano-carriers were stable in serum-containing media without forming any aggregation and did not show any acute cytotoxicity to both normal (NIH3T3 fibroblast) and tumor (SCC7) cells. Chitosan conjugation did not change their sizes or thermo-sensitive properties of the nano-carriers, but significantly increased their in-vitro cellular uptake compared to the corresponding bare forms. The in-vivo tumor accumulation of these nano-carriers was optically monitored by using Cy5.5-attached nano-carriers in SCC7 tumor-bearing mice. For all cases, local accumulation of the injected nano-carriers in liver was not dominant compared to the tumor site, demonstrating good tumor targeting efficacy of the Pluronic-based nano-carriers. Among different samples, chitosan-conjugated nano-carriers showed much better tumor accumulation than bare forms, and mostly remained up to 72h, implying prolonged blood circulation and more efficient tumor accumulation. Between Chito-NC(PF 68) and Chito-NC(PF 127), Chito-NC(PF 68) showed a little better tumor accumulation and retention, suggesting the difference in Pluronic, thus difference in hydrophilicity and the size of the nano-carriers also might affect the tumor targeting. In contrast, bare nano-carriers were initially accumulated well in tumor, but they were excreted from the tumor site relatively rapidly. Therefore, chitosan-functionalization was very effective for improving the tumor targeting efficacy of Pluronic-based nano-carriers.
基于普朗尼克的纳米载体，包括由普朗尼克 F68（NC（PF68））或普朗尼克 F127（NC（PF127））组成的裸形式，以及壳聚糖接枝形式（Chito-NC（PF68）或 Chito-NC（PF127）），通过光聚合两种二丙烯酰化普朗尼克（F68 和 F127）和丙烯酰化壳聚糖来制备，以研究壳聚糖接枝及其物理化学特性（大小和亲水性）对基于普朗尼克的纳米载体的肿瘤靶向效率的影响。所有纳米载体在含血清的介质中均稳定，不会形成任何聚集，并且对正常（NIH3T3 成纤维细胞）和肿瘤（SCC7）细胞均没有显示出任何急性细胞毒性。壳聚糖接枝不会改变纳米载体的大小或温敏特性，但与相应的裸形式相比，可显著增加其体外细胞摄取。通过在 SCC7 荷瘤小鼠中使用 Cy5.5 附着的纳米载体来光学监测这些纳米载体在体内的肿瘤积累。对于所有情况，与肿瘤部位相比，注射的纳米载体在肝脏中的局部积累并不占主导地位，这表明基于普朗尼克的纳米载体具有良好的肿瘤靶向效率。在不同的样品中，壳聚糖接枝的纳米载体比裸形式具有更好的肿瘤积累，并且大部分在 72 小时内仍然存在，这意味着延长了血液循环时间和更有效的肿瘤积累。在 Chito-NC（PF68）和 Chito-NC（PF127）之间，Chito-NC（PF68）显示出更好的肿瘤积累和保留，这表明普朗尼克的差异，因此亲水性和纳米载体的大小的差异也可能影响肿瘤靶向。相比之下，裸纳米载体最初在肿瘤中积累良好，但它们从肿瘤部位迅速排出。因此，壳聚糖功能化对于提高基于普朗尼克的纳米载体的肿瘤靶向效率非常有效。
