透明质酸酶响应型靶向纳米粒用于结肠癌中 5-氟尿嘧啶的有效递送
Hyaluronidase Enzyme-responsive Targeted Nanoparticles for Effective Delivery of 5-Fluorouracil in Colon Cancer.
机构信息
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
North Administration Office, Affiliated Hospital of Qingdao University, Qingdao, 26600, China.
出版信息
Pharm Res. 2018 Feb 23;35(4):73. doi: 10.1007/s11095-017-2302-4.
PURPOSE
In this study, we have successfully prepared the hyaluronic acid (HA)-conjugated mesoporous silica nanoparticles loaded with 5-fluorouracil (5-FU) to increase the anticancer efficacy in colon cancers.
METHODS
The particles were nanosized and perfectly spherical. In vitro release kinetics clearly showed the enzyme-sensitive release of 5-FU from HA-conjugated 5-FU loaded mesoporous silica nanoparticles (HA/FMSN).
RESULTS
The presence of HA on the surface of nanoparticles targeted the CD44 receptors overexpressed in the colon cancer cells In vitro cell viability and apoptosis assay clearly showed the superior anticancer effect of HA/FMSN in HT29 colon cancer cells. HA/FMSN exhibited a remarkably higher 43% of cells in early apoptosis phase and 55% of cells in late apoptosis phase indicating the superior anticancer effect of HA/FMSN. HA/FMSN exhibited a significant reduction in the tumor burden compared to that of any group. HA/FMSN was 3-fold more effective than free drug and 2-fold more effective than -FU loaded mesoporous silica nanoparticles (FMSN).
CONCLUSIONS
Overall, results suggest that the novel delivery strategy could hold enormous potential in colon cancer targeting.
目的
本研究成功制备了透明质酸（HA）偶联载 5-氟尿嘧啶（5-FU）的介孔硅纳米粒子，以提高结肠癌的抗癌疗效。
方法
粒子呈纳米级且呈完美球形。体外释放动力学清楚地表明，HA 偶联载 5-FU 的介孔硅纳米粒子（HA/FMSN）中 5-FU 具有酶敏感释放特性。
结果
纳米粒子表面存在的 HA 靶向了在结肠癌细胞中过表达的 CD44 受体。体外细胞活力和凋亡试验清楚地表明，HA/FMSN 在 HT29 结肠癌细胞中具有更好的抗癌作用。HA/FMSN 使早期凋亡阶段的细胞增加了 43%，晚期凋亡阶段的细胞增加了 55%，表明 HA/FMSN 的抗癌作用更强。与任何组相比，HA/FMSN 显著降低了肿瘤负担。HA/FMSN 的效果是游离药物的 3 倍，是载有 5-FU 的介孔硅纳米粒子（FMSN）的 2 倍。
结论
总体而言，结果表明，这种新的递药策略在结肠癌靶向治疗方面具有巨大的潜力。
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