Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis.
Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe(3)O(4) 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.
Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung Memorial Hospital, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China.
Hung-Wei
HW
Yang
Mu-Yi
MY
Hua
Kun-Ju
KJ
Lin
Shiaw-Pyng
SP
Wey
Rung-Ywan
RY
Tsai
Siao-Yun
SY
Wu
Yi-Ching
YC
Lu
Hao-Li
HL
Liu
Tony
T
Wu
Yunn-Hwa
YH
Ma
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D008422:Materials Testing; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000737:chemistry*
D005343:Fibrinolytic Agents; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D010959:Tissue Plasminogen Activator