College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
J Control Release. 2016 Aug 28;236:38-46. doi: 10.1016/j.jconrel.2016.06.021. Epub 2016 Jun 16.
Dual CD44 and folate receptor targetable nanoparticles (NPs) based on hyaluronic acid-ceramide-folic acid (HACE-FA) were fabricated for improving tumor targetability. HACE-FA was synthesized via esterification between the carboxylic group of FA and hydroxyl group of HA. Doxorubicin (DOX)-loaded HACE-FA NPs, with a mean diameter of 120-130nm, narrow size distribution, and negative zeta potential, were prepared. The drug release from HACE-FA NPs were significantly increased in acidic pH (pH5.5) compared with physiological pH (7.4) (p<0.05). The cellular accumulation of the drug in HACE-FA NPs group was higher than that of HACE NPs group in SKOV-3 cells (human ovarian cancer cells; CD44 and folate receptor (FR)-positive cells). Dual targetability of HACE-FA NPs, compared to HACE NPs, was also verified in the SKOV-3 tumor-xenografted mouse model by near-infrared fluorescence (NIRF) imaging. Twenty-four hours after injection, HACE-FA NPs were accumulated mainly in tumor regions and their fluorescence intensity was 4.82-fold higher than that of HACE NPs (p<0.05). These findings suggest successful application of HACE-FA NPs for the accurate delivery of anticancer drugs to ovarian cancer.
基于透明质酸-神经酰胺-叶酸（HACE-FA）的双靶向 CD44 和叶酸受体的纳米粒子（NPs）被制备用于提高肿瘤靶向性。HACE-FA 通过 FA 的羧基和 HA 的羟基之间的酯化反应合成。载阿霉素（DOX）的 HACE-FA NPs 的平均直径为 120-130nm，具有较窄的粒径分布和负的 zeta 电位。与生理 pH（7.4）相比，HACE-FA NPs 在酸性 pH（pH5.5）下的药物释放明显增加（p<0.05）。与 HACE NPs 相比，HACE-FA NPs 组在 SKOV-3 细胞（人卵巢癌细胞；CD44 和叶酸受体（FR）阳性细胞）中的药物细胞积累更高。在 SKOV-3 肿瘤异种移植小鼠模型中，通过近红外荧光（NIRF）成像也验证了 HACE-FA NPs 的双重靶向性。注射后 24 小时，HACE-FA NPs 主要积聚在肿瘤区域，其荧光强度比 HACE NPs 高 4.82 倍（p<0.05）。这些发现表明 HACE-FA NPs 成功地应用于将抗癌药物精确递送到卵巢癌。
