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Dual CD44 and folate receptor-targeted nanoparticles for cancer diagnosis and anticancer drug delivery.

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.
AuthorsJae-Young Lee, Ubonvan Termsarasab, Ju-Hwan Park, Song Yi Lee, Seung-Hak Ko, Jae-Seong Shim, Suk-Jae Chung, Hyun-Jong Cho, Dae-Duk Kim
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 236 Pg. 38-46 (08 28 2016) ISSN: 1873-4995 [Electronic] Netherlands
PMID27320169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2016 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Ceramides
  • Drug Carriers
  • Folate Receptors, GPI-Anchored
  • Hyaluronan Receptors
  • Doxorubicin
  • Hyaluronic Acid
  • Folic Acid
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage)
  • Cell Line, Tumor
  • Ceramides (chemistry)
  • Doxorubicin (administration & dosage)
  • Drug Carriers
  • Drug Liberation
  • Female
  • Folate Receptors, GPI-Anchored (metabolism)
  • Folic Acid (chemistry)
  • Humans
  • Hyaluronan Receptors (metabolism)
  • Hyaluronic Acid (chemistry)
  • Mice
  • Molecular Targeted Therapy
  • Nanoparticles (chemistry)
  • Optical Imaging
  • Ovarian Neoplasms (diagnosis, drug therapy)
  • Particle Size

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