Self-assembled hyaluronic acid nanoparticles as a potential drug carrier for cancer therapy: synthesis, characterization, and in vivo biodistribution
Self-assembled hyaluronic acid nanoparticles as a potential drug carrier for cancer therapy: synthesis, characterization, and in vivo biodistribution
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DOI：
10.1039/b900456d
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Jeong, Seo Young
中科院分区：
文献类型：
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作者：
Choi, Ki Young;Min, Kyung Hyun;Jeong, Seo Young
为了开发用于癌症治疗的纳米级药物递送系统，通过将疏水性 5β-胆烷酸化学缀合到透明质酸 (HA) 的主链来合成两亲性透明质酸缀合物。 HA缀合物可以在生理条件下（PBS，pH 7.4，37℃）通过5个β-胆酸之间的疏水相互作用形成纳米尺寸的自聚集体。 HA纳米颗粒呈球形，尺寸在350-400 nm范围内，具体取决于5β-胆酸的取代程度。使用 Cy5.5 标记的 HA 纳米颗粒进行的细胞实验表明，它们可以被过度表达 CD44（HA 受体）的 SCC7 癌细胞有效吸收。当Cy5.5标记的HA纳米颗粒被全身注射到荷瘤小鼠的尾静脉中时，大多数纳米颗粒出现在肿瘤和肝脏部位。特别是，纳米粒子在肿瘤部位的荧光强度比纯HA聚合物高4倍，这一点被非侵入性近红外荧光成像系统证实。 HA纳米粒子的高肿瘤靶向能力可能源于其在血液中的长时间循环和与肿瘤细胞的高亲和力。这些结果揭示了HA纳米颗粒作为稳定有效的纳米药物输送系统用于癌症治疗的巨大潜力。
To develop a nano-sized drug delivery system for cancer therapy, amphiphilic hyaluronic acid conjugates were synthesized by chemical conjugation of hydrophobic 5 beta-cholanic acid to the backbone of hyaluronic acid (HA). The HA conjugates could form nano-sized self-aggregates under physiological conditions (PBS, pH 7.4, 37 degrees C) via the hydrophobic interaction among 5 beta-cholanic acids. The HA nanoparticles were spherical in shape and their sizes were in the range of 350-400 nm, depending on the degree of substitution of 5 beta-cholanic acid. From a cellular experiment using Cy5.5-labeled HA nanoparticles, it was demonstrated that they are efficiently taken up by SCC7 cancer cells which over-express CD44, the receptor for HA. When the Cy5.5-labeled HA nanoparticles were systemically administrated into the tail vein of tumor-bearing mice, most of the nanoparticles were found in tumor and liver sites. In particular, the fluorescence intensity of nanoparticles at the tumor site was 4-fold higher than that of pure HA polymer, which was confirmed by a non-invasive near-infrared fluorescence imaging system. The high tumor targeting ability of HA nanoparticles might result from both their prolonged circulation in blood and high affinity to tumor cells. These results reveal the promising potential of HA nanoparticles as a stable and effective nano-sized drug delivery system for cancer treatment.