Targeted thrombolysis of tissue plasminogen activator and streptokinase with extracellular biosynthesis nanoparticles using optimized Streptococcus equi supernatant

Tadayon, Ateke; Jamshidi, Reza; Esmaeili, Akbar

doi:10.1016/j.ijpharm.2016.02.011

Cited by 22 publications

(12 citation statements)

References 16 publications

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“…In this study, the sizes of 4-PEG(G 3 ) 4 , NK and 4-PEG(G 3 ) 4 /NK (1/1) were observed by DLS, and the results were shown in Figure 5. From the results of DLS, we can see that the size of 4-PEG(G 3 ) 4 and NK is 62 and 45 nm, respectively, which correlates very well with the size of 4-PEG(G 3 ) 4 and NK particles measured by TEM. The size of 4-PEG(G 3 ) 4 /NK (1/1) is 105 nm.…”

Section: Dls and Tem Determination Of 4-peg(g 3 ) 4 /Nksupporting

confidence: 72%

“…Moreover, these 4-PEG(G 3 ) 4 /NK (1/1) compositions were safe when injected into the body due to their small size of <500 nm. NK can reach the blood clots through blood circulation, and then dissolve thrombus by breaking electrostatic interaction with 4-PEG(G 3 ) 4 . Therefore, 4-PEG(G 3 ) 4 /NK (1/1) has great potential for applications in the treatment of thrombotic patients.…”

Section: Dls and Tem Determination Of 4-peg(g 3 ) 4 /Nkmentioning

confidence: 99%

“…Many thrombotic diseases, including the deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction, are the result of the formation of thrombus . Thrombolytic therapy is considered to be a very promising approach to treat thrombotic disease, which is based on the administration of thrombolytic drugs that activate the proenzyme plasminogen to plasmin and cleave fibrin into soluble degradation products . However, the various thrombolytic drugs used clinically have complications, a short half‐life in plasma and the tendency to cause hemorrhage.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Thrombolytic therapy is considered to be a very promising approach to treat thrombotic disease, which is based on the administration of thrombolytic drugs that activate the proenzyme plasminogen to plasmin and cleave fibrin into soluble degradation products. 4,5 However, the various thrombolytic drugs used clinically have complications, a short half-life in plasma and the tendency to cause hemorrhage. Thrombolytic drugs without these disadvantages are needed.…”

Section: Introductionmentioning

confidence: 99%

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Multiarm‐polyethylene glycol‐polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus

Zhang

Lü

Gao

et al. 2018

J Biomedical Materials Res

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Thrombotic events affect many individuals in a number of ways, all of which can cause significant morbidity and mortality. Nattokinase (NK), as a novel thrombolytic drug, has been used for thrombolytic therapy. It not only possesses plasminogen activator activity, but also directly digests fibrin through limited proteolysis. However, it may undergo inactivation and denaturation in the harsh external environment. In this study, a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer was fabricated and used as a carrier for NK protection and delivery. Different arm numbers of polyethylene glycol-polyglutamic acid peptide dendrimers (x-PEG(G ) , x = 2, 4, 6, 8) were designed, prepared, and characterized by H NMR and FTIR. Then, x-PEG(G ) were loaded with NK to form nanocomposites. Their size and morphology were determined by dynamic light scattering and transmission electron microscopy. Enzyme activity was evaluated via UV-Vis absorbance spectra, fluorescence spectra, circular dichroism spectra, and zeta potential measurements. The study reveals that the obtained x-PEG(G ) /NK nanocomposites possess high enzyme activity. In addition, the nanocomposites show increased viability of rat macrophage cells, and excellent thrombolysis ability in vitro and in vivo. This work establishes a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer with potential application in NK carrier and thrombolytic therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1687-1696, 2018.

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Section: Dls and Tem Determination Of 4-peg(g 3 ) 4 /Nksupporting

confidence: 72%

Section: Dls and Tem Determination Of 4-peg(g 3 ) 4 /Nkmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multiarm‐polyethylene glycol‐polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus

Zhang

Lü

Gao

et al. 2018

J Biomedical Materials Res

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show abstract

“…This novel hybrid cell microvesicles could be manipulated by magnetic force for targeting delivery of tPA to blood clots 47 . Lately, Tadayon et al developed an extracellular biosynthesis of nanoparticles (CuNP) for the simultaneously targeted delivery of tPA and streptokinase (SK) 48 . tPA and SK were conjugated with these CuNP nanoparticles.…”

Section: Nanocarriers For Tpamentioning

confidence: 99%

Tissue plasminogen activator-based nanothrombolysis for ischemic stroke

Liu

Feng

Jin

et al. 2017

Expert Opinion on Drug Delivery

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Introduction Thrombolysis with intravenous tissue plasminogen activator (tPA) is the only FDA approved treatment for patients with acute ischemic stroke, but its use is limited by narrow therapeutic window, selective efficacy, and hemorrhagic complication. In the past two decades, extensive efforts have been undertaken to extend its therapeutic time window and explore alternative thrombolytic agents, but both show little progress. Nanotechnology has emerged as a promising strategy to improve the efficacy and safety of tPA. Areas covered We reviewed the biology, thrombolytic mechanism, and pleiotropic functions of tPA in the brain and discussed current applications of various nanocarriers intended for the delivery of tPA for treatment of ischemic stroke. Current challenges and potential further directions of t-PA-based nanothrombolysis in stroke therapy are also discussed. Expert opinion Using nanocarriers to deliver tPA offers many advantages to enhance the efficacy and safety of tPA therapy. Further research is needed to characterize the physicochemical characteristics and in vivo behavior of tPA-loaded nanocarriers. Combination of tPA based nanothrombolysis and neuroprotection represents a promising treatment strategy for acute ischemic stroke. Theranostic nanocarriers co-delivered with tPA and imaging agents are also promising for future stroke management.

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Synthesis of mesoporous silica/polyglutamic acid peptide dendrimer with dual targeting and its application in dissolving thrombus

Huang

Zhang

Lü

et al. 2019

J Biomedical Materials Res

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With the frequent occurrence of thrombus diseases, thrombus has become a factor endangering human health. Nattokinase (NK) is a new generation of thrombolytic drug with efficient thrombolytic effect and no major side effects. However, it is easily inactivated in external environment due to its sensitivity, which is still a challenge for its generalized application. Herein, a mesoporous silica/polyglutamic acid peptide dendrimer (M‐MSNs‐G3‐RGD) nanoparticle was prepared to protect and transport NK. First, magnetic mesoporous silica nanoparticles (M‐MSNs) were prepared as the core of the whole nanoparticle, then polyglutamic acid peptide dendrimer (G3) was bonded to form M‐MSNs‐G3. At last, arginine‐glycine‐aspartic peptide (RGD) was grafted onto the M‐MSNs‐G3 to obtain M‐MSNs‐G3‐RGD. The physical and chemical characteristics and biological toxicity of M‐MSNs‐G3‐RGD were studied. Thrombus‐targeting nanocomposites M‐MSNs‐G3‐RGD/NK were prepared by loading the thrombolytic drug NK via electrostatic interaction. In vitro and in vivo targeted thrombolytic experiments showed that the nanoparticles exhibited significant thrombolysis ability. These results suggested the potential application of M‐MSNs‐G3‐RGD/NK in dual targeted thrombolysis.

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Targeted thrombolysis of tissue plasminogen activator and streptokinase with extracellular biosynthesis nanoparticles using optimized Streptococcus equi supernatant

Cited by 22 publications

References 16 publications

Multiarm‐polyethylene glycol‐polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus

Multiarm‐polyethylene glycol‐polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus

Tissue plasminogen activator-based nanothrombolysis for ischemic stroke

Synthesis of mesoporous silica/polyglutamic acid peptide dendrimer with dual targeting and its application in dissolving thrombus

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