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Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Authors Sudha T, Bharali DJ, Yalcin M, Darwish NHE, Debreli Coskun M, Keating KA, Lin HY, Davis PJ, Mousa SA

Received 3 October 2016

Accepted for publication 28 November 2016

Published 15 February 2017 Volume 2017:12 Pages 1305—1315

DOI https://doi.org/10.2147/IJN.S123742

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Professor Carlos Rinaldi


Thangirala Sudha,1 Dhruba J Bharali,1 Murat Yalcin,1,2 Noureldien HE Darwish,1,3 Melis Debreli Coskun,1,4 Kelly A Keating,1 Hung-Yun Lin,5,6 Paul J Davis,1,7 Shaker A Mousa1

1The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; 2Department of Physiology, Veterinary Medicine Faculty, Uludag University, Gorukle, Bursa, Turkey; 3Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 4Department of Biology, Faculty of Arts and Sciences, Uludag University, Gorukle, Bursa, Turkey; 5PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, 6Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; 7Department of Medicine, Albany Medical College, Albany, NY, USA

Abstract:
The tetraiodothyroacetic acid (tetrac) component of nano-diamino-tetrac (NDAT) is chemically bonded via a linker to a poly(lactic-co-glycolic acid) nanoparticle that can encapsulate anticancer drugs. Tetrac targets the plasma membrane of cancer cells at a receptor on the extracellular domain of integrin αvβ3. In this study, we evaluate the efficiency of NDAT delivery of paclitaxel and doxorubicin to, respectively, pancreatic and breast cancer orthotopic nude mouse xenografts. Intra-tumoral drug concentrations were 5-fold (paclitaxel; P<0.001) and 2.3-fold (doxorubicin; P<0.01) higher than with conventional systemic drug administration. Tumor volume reductions reflected enhanced xenograft drug uptake. Cell viability was estimated by bioluminescent signaling in pancreatic tumors and confirmed an increased paclitaxel effect with drug delivery by NDAT. NDAT delivery of chemotherapy increases drug delivery to cancers and increases drug efficacy.

Keywords: doxorubicin, integrin, nanoparticle, Nanotetrac, NDAT, paclitaxel, tetraiodothyroacetic acid, xenografts

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