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Abstract

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. 

Author information

Lee JY1, Termsarasab U1, Park JH1, Lee SY2, Ko SH3, Shim JS4, Chung SJ1, Cho HJ5, Kim DD6.​

1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.

2College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.

3Biogenics Inc., Daejeon 305-510, Republic of Korea.

4Biogenics Inc., Daejeon 305-510, Republic of Korea; Skin & Tech Inc., Seongnam 461-713, Republic of Korea.

5College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.

6College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ddkim@snu.ac.kr.