Effective targeting of gemcitabine to pancreatic cancer through PEG-cored Flt-1 antibody-conjugated dendrimers

Ozturk K., ESENDAĞLI G., Gurbuz M. U., TÜLÜ M., ÇALIŞ S.

INTERNATIONAL JOURNAL OF PHARMACEUTICS, cilt.517, ss.157-167, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 517
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.ijpharm.2016.12.009
  • Dergi Adı: INTERNATIONAL JOURNAL OF PHARMACEUTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.157-167
  • Anahtar Kelimeler: Dendrimers, Pancreatic cancer, Targeted drug delivery, Gemcitabine, Cell culture, Tumor-bearing mice, ENDOTHELIAL GROWTH-FACTOR, PHASE-III TRIAL, PAMAM DENDRIMERS, DRUG-DELIVERY, BREAST-CANCER, POLY(AMIDOAMINE) DENDRIMERS, BIOMEDICAL APPLICATIONS, DESIGNING DENDRIMERS, SURFACE MODIFICATION, THERAPY
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Tumor-targeted delivery of anticancer drugs using dendrimers has been recognized as a promising strategy to increase efficiency and reduce adverse effects of chemotherapy. Herein, we developed a dendrimer-based drug delivery system targeting Flt-1 (a receptor for vascular endothelial growth factors (VEGF)) receptor to improve therapeutic efficacy of gemcitabine in pancreatic cancer. Synthesized polyethylene glycol (PEG)-cored PAMAM dendrimers, which bear anionic carboxylic acid groups on the surface were modified with PEG chains, which were then conjugated with Flt-1 antibody. Following structural and chemical characterization studies, gemcitabine HCl-dendrimer inclusion complexes were successfully prepared. These complexes were efficiently engulfed by Fit-i expressing pancreatic cancer cells, which enhanced the cytotoxicity of gemcitabine. Moreover, pancreatic tumors established in mice were highly targeted by PEG-cored Flt-1 antibody-conjugated dendrimers and increased accumulation of these gemcitabine-loaded complexes exhibited satisfactory in vivo anti-cancer efficacy. In conclusion, dendrimer-based targeted delivery of chemotherapeutics may serve as a promising approach for the treatment of malignancies such as pancreatic cancer that do not benefit from conventional chemotherapy. (C) 2016 Elsevier B.V. All rights reserved.