Dual CD44 and folate receptor-targeted nanoparticles for cancer diagnosis and anticancer drug delivery.
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.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Jae-Young
JY
Lee
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Ubonvan
U
Termsarasab
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Ju-Hwan
JH
Park
College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Song Yi
SY
Lee
Biogenics Inc., Daejeon 305-510, Republic of Korea.
Seung-Hak
SH
Ko
Biogenics Inc., Daejeon 305-510, Republic of Korea; Skin & Tech Inc., Seongnam 461-713, Republic of Korea.
Jae-Seong
JS
Shim
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Suk-Jae
SJ
Chung
College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.
Hyun-Jong
HJ
Cho
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ddkim@snu.ac.kr.
Dae-Duk
DD
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D065546:Drug Liberation; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D010316:Particle Size
D000970:Antineoplastic Agents; D002518:Ceramides; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D018960:Hyaluronan Receptors; D004317:Doxorubicin; D006820:Hyaluronic Acid; D005492:Folic Acid
CD44 receptor; Dual targeting; Folate receptor; Hyaluronic acid-ceramide-folic acid; Nanoparticles