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

ABSTRACT: 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.

SUBMITTER: Yang HW

PROVIDER: S-EPMC3464084 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Yang Hung-Wei HW Hua Mu-Yi MY Lin Kun-Ju KJ Wey Shiaw-Pyng SP Tsai Rung-Ywan RY Wu Siao-Yun SY Lu Yi-Ching YC Liu Hao-Li HL Wu Tony T Ma Yunn-Hwa YH

International journal of nanomedicine 20121001

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 an ...[more]

PMID: 23055728

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Project description:ObjectivesThe benefit of intravenous recombinant tissue plasminogen activator (rt-PA) therapy for very old patients with acute ischemic stroke remains unclear. The aim of this study was to elucidate the efficacy and safety of intravenous rt-PA therapy for patients over 80 years old.MethodsOf 13,521 stroke patients registered in the Fukuoka Stroke Registry in Japan from June 1999 to February 2013, 953 ischemic stroke patients who were over 80 years old, hospitalized within 3 h of onset, and not treated with endovascular therapy were included in this study. Among them, 153 patients were treated with intravenous rt-PA (0.6 mg/kg). For propensity score (PS)-matched case-control analysis, 148 patients treated with rt-PA and 148 PS-matched patients without rt-PA therapy were selected by 1:1 matching with propensity for using rt-PA. Clinical outcomes were neurological improvement, good functional outcome at discharge, in-hospital mortality, and hemorrhagic complications (any intracranial hemorrhage [ICH], symptomatic ICH, and gastrointestinal bleeding).ResultsIn the full cohort of 953 patients, rt-PA use was associated positively with neurological improvement and good functional outcome, and negatively with in-hospital mortality after adjustment for multiple confounding factors. In PS-matched case-control analysis, patients treated with rt-PA were still at lower risk for unfavorable clinical outcomes than non-treated patients (neurological improvement, odds ratio 2.67, 95% confidence interval 1.61-4.40; good functional outcome, odds ratio 2.23, 95% confidence interval 1.16-4.29; in-hospital mortality, odds ratio 0.30, 95% confidence interval 0.13-0.65). There was no significant association between rt-PA use and risk of hemorrhagic complications in the full and PS-matched cohorts.ConclusionsIntravenous rt-PA therapy was associated with improved clinical outcomes without significant increase in risk of hemorrhagic complications in very old patients (aged>80 years) with acute ischemic stroke.

Dataset Information

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

Publications

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

Similar Datasets

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