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author：

Yin, J.-J. (Yin, J.-J..) [1] | Sharma, S. (Sharma, S..) [2] | Shumyak, S.P. (Shumyak, S.P..) [3] | Wang, Z.-X. (Wang, Z.-X..) [4] | Zhou, Z.-W. (Zhou, Z.-W..) [5] | Zhang, Y. (Zhang, Y..) [6] | Guo, P. (Guo, P..) [7] | Li, C.-Z. (Li, C.-Z..) [8] | Kanwar, J.R. (Kanwar, J.R..) [9] | Yang, T. (Yang, T..) [10] | Mohapatra, S.S. (Mohapatra, S.S..) [11] | Liu, W. (Liu, W..) [12] | Duan, W. (Duan, W..) [13] | Wang, J.-C. (Wang, J.-C..) [14] | Li, Q. (Li, Q..) [15] | Zhang, X. (Zhang, X..) [16] | Tan, J. (Tan, J..) [17] | Jia, L. (Jia, L..) [18] | Liang, J. (Liang, J..) [19] | Wei, M.Q. (Wei, M.Q..) [20] | Li, X. (Li, X..) [21] | Zhou, S.-F. (Zhou, S.-F..) [22]

Indexed by：

Scopus

Abstract：

Drug　targeting　is　an　active　area　of　research　and　nano-scaled　drug　delivery　systems　hold　tremendous　potential　for　the　treatment　of　neoplasms.　In　this　study,　a　novel　cyclodextrin　(CD)-based　nanoparticle　drug　delivery　system　has　been　assembled　and　characterized　for　the　therapy　of　folate　receptor-positive　[FR(+)]　cancer.　Water-soluble　folic　acid　(FA)-conjugated　CD　carriers　(FACDs)　were　successfully　synthesized　and　their　structures　were　confirmed　by　1D/2D　nuclear　magnetic　resonance　(NMR),　matrix-assisted　laser　desorption　ionization　time-of-flight　mass　spectrometer　(MALDI-TOF-MS),　high　performance　liquid　chromatography　(HPLC),　Fourier　transform　infrared　spectroscopy　(FTIR),　and　circular　dichroism.　Drug　complexes　of　adamatane　(Ada)　and　cytotoxic　doxorubicin　(Dox)　with　FACD　were　readily　obtained　by　mixed　solvent　precipitation.　The　average　size　of　FACD-Ada-Dox　was　1.5-2.5　nm.　The　host-guest　association　constant　Ka　was　1,639　M-1　as　determined　by　induced　circular　dichroism　and　the　hydrophilicity　of　the　FACDs　was　greatly　enhanced　compared　to　unmodified　CD.　Cellular　uptake　and　FR　binding　competitive　experiments　demonstrated　an　efficient　and　preferentially　targeted　delivery　of　Dox　into　FR-positive　tumor　cells　and　a　sustained　drug　release　profile　was　seen　in　vitro.　The　delivery　of　Dox　into　FR(+)　cancer　cells　via　endocytosis　was　observed　by　confocal　microscopy　and　drug　uptake　of　the　targeted　nanoparticles　was　8-fold　greater　than　that　of　non-targeted　drug　complexes.　Our　docking　results　suggest　that　FA,　FACD　and　FACD-Ada-Dox　could　bind　human　hedgehog　interacting　protein　that　contains　a　FR　domain.　Mouse　cardiomyocytes　as　well　as　fibroblast　treated　with　FACD-Ada-Dox　had　significantly　lower　levels　of　reactive　oxygen　species,　with　increased　content　of　glutathione　and　glutathione　peroxidase　activity,　indicating　a　reduced　potential　for　Dox-induced　cardiotoxicity.　These　results　indicate　that　the　targeted　drug　complex　possesses　high　drug　association　and　sustained　drug　release　properties　with　good　biocompatibility　and　physiological　stability.　The　novel　FA-conjugated　β-CD　based　drug　complex　might　be　promising　as　an　anti-tumor　treatment　for　FR(+)　cancer.　©　2013　Yin　et　al.

Keyword：

Community：

  • [ 1 ] [Yin, J.-J.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States
  • [ 2 ] [Sharma, S.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States
  • [ 3 ] [Shumyak, S.P.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States
  • [ 4 ] [Wang, Z.-X.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States
  • [ 5 ] [Zhou, Z.-W.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States
  • [ 6 ] [Zhang, Y.]National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
  • [ 7 ] [Guo, P.]Nanobiotechnology Center and Markey Cancer Center, College of Pharmacy, Unsiversity of Kentucky, Lexington, KY, United States
  • [ 8 ] [Li, C.-Z.]Nanobioengineering and Bioelectronics Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL, United States
  • [ 9 ] [Kanwar, J.R.]Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (LIMBR), Centre for Biotechnology and Interdisciplinary Biosciences and Inst. for Frontier Materials (IFM), Deakin University, Waurn Ponds, VIC, Australia
  • [ 10 ] [Yang, T.]Department of Internal Medicine, University of Utah, Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, United States
  • [ 11 ] [Mohapatra, S.S.]Nanomedicine Research Center and Division of Translational Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
  • [ 12 ] [Liu, W.]Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, United States
  • [ 13 ] [Duan, W.]School of Medicine, Deakin University, Waurn Ponds, VIC, Australia
  • [ 14 ] [Wang, J.-C.]State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing, China
  • [ 15 ] [Li, Q.]Department of Oncology, Shuguang Hospital (Western Campus), Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • [ 16 ] [Zhang, X.]Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, China
  • [ 17 ] [Tan, J.]James A. Haley Veterans' Administration Hospital, Tampa, FL, United States
  • [ 18 ] [Tan, J.]Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
  • [ 19 ] [Tan, J.]Department of Psychiatry and Behavioral Neurosciences, Silver Child Development Center, Rashid Laboratory for Developmental Neurobiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
  • [ 20 ] [Jia, L.]Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou, China
  • [ 21 ] [Liang, J.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States
  • [ 22 ] [Wei, M.Q.]School of Medical Science, Division of Molecular and Gene Therapies, Griffith Health Institute, Griffith University, Gold Coast Campus, Australia
  • [ 23 ] [Li, X.]Obstetrics and Gynecology Hospital and Institute of Biomedicine, Fudan University, Shanghai, China
  • [ 24 ] [Zhou, S.-F.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States

Reprint 's Address：

  • [Zhou, S.-F.]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, United States

Email：


szhou@health.usf.edu
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Source ：

PLoS ONE

ISSN： 1932-6203

Year： 2013

Issue： 5

Volume： 8

3 . 5 3 4

JCR@2013

2 . 9 0 0

JCR@2023

JCR Journal Grade：1

CAS Journal Grade：3

Cited Count：

WoS CC Cited Count：

SCOPUS Cited Count：

ESI Highly Cited Papers on the List： 0 Unfold All

WanFang Cited Count：

Chinese Cited Count：

30 Days PV： 2

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