Back to Journals » International Journal of Nanomedicine » Volume 7

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

Authors Yang HW, Hua MY, Lin KJ, Wey SP, Tsai RY, Wu SY, Lu YC, Liu HL, Wu T, Ma YH

Received 13 April 2012

Accepted for publication 5 July 2012

Published 1 October 2012 Volume 2012:7 Pages 5159—5173

DOI https://doi.org/10.2147/IJN.S32939

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Hung-Wei Yang,1,* Mu-Yi Hua,1,* Kun-Ju Lin,2,* Shiaw-Pyng Wey,3 Rung-Ywan Tsai,4 Siao-Yun Wu,5 Yi-Ching Lu,5 Hao-Li Liu,6 Tony Wu,7 Yunn-Hwa Ma5

1Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, 2Molecular Imaging Center, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 3Department of Medical Imaging and Radiological Sciences, 4Electronics and Optoelectronics Research Laboratories, Industrial Technology Research Institute, Hsin-chu, Taiwan, Republic of China; 5Department of Physiology and Pharmacology and Healthy Aging Research Center, 6Department of Electrical Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 7Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, Tao-Yuan, Taiwan, Republic of China

*These authors contributed equally to this work

Abstract: Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 µg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15–25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.

Keywords: thrombolysis, recombinant tissue plasminogen activator, magnetic nanocarriers, magnetic targeting, targeting therapy

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Readers of this article also read:

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

Chen DZ, Tang QS, Li XD, Zhou XJ, Zang J, Xue WQ, Xiang JY, Guo CQ

International Journal of Nanomedicine 2012, 7:4973-4982

Published Date: 14 September 2012

Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells

Zhang Y, Huang Y, Zhang P, Gao X, Gibbs RB, Li S

International Journal of Nanomedicine 2012, 7:4473-4485

Published Date: 13 August 2012

Biofunctionalization of a titanium surface with a nano-sawtooth structure regulates the behavior of rat bone marrow mesenchymal stem cells

Zhang WJ, Li ZH, Liu Y, Ye DX, Li JH, Xu LY, Wei B, Zhang XL, Liu XY, Jiang XQ

International Journal of Nanomedicine 2012, 7:4459-4472

Published Date: 13 August 2012

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Riggio C, Calatayud MP, Hoskins C, Pinkernelle J, Sanz B, Torres TE, Ibarra MR, Wang L, Keilhoff G, Goya GF, Raffa V, Cuschieri A

International Journal of Nanomedicine 2012, 7:3155-3166

Published Date: 25 June 2012

Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo

Li Y, Liu J, Zhong Y, Zhang J, Wang Z, Wang L, An Y, Lin M, Gao Z, Zhang D

International Journal of Nanomedicine 2011, 6:2805-2819

Published Date: 9 November 2011

Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system

Estevanato L, Cintra D, Baldini N, Portilho F, Barbosa L, Martins O, Lacava B, Miranda-Vilela AL, Tedesco AC, Báo S, Morais PC, Lacava ZGM

International Journal of Nanomedicine 2011, 6:1709-1717

Published Date: 18 August 2011