Streptokinase@alumina nanoparticles as a promising thrombolytic colloid with prolonged action

Chapurina, Yulia; Drozdov, Andrey S.; Popov, Inna; Виноградов, В. В.; Dudanov, I P; Vinogradov, Vladimir V.

doi:10.1039/c6tb01349j

Cited by 28 publications

(14 citation statements)

References 30 publications

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“…Static in vitro thrombolysis in vertical position, using a blood clot made from rat whole blood, was performed with or without a magnet, to determine the effectiveness of magnetic targeting in blood clot lysis (Figure 10a) [51]. For this purpose, the extent of clot lysis when pre-formed blood clot was treated by rtPA and PMNP-rtPA in a sample tube was compared under the influence of downward magnetic pulling force generated from a magnet placed at the bottom of the tube.…”

Section: In Vitro Thrombolysismentioning

confidence: 99%

Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy

Chen

Hsu

et al. 2020

IJMS

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Recombinant tissue plasminogen activator (rtPA) is the only thrombolytic agent that has been approved by the FDA for treatment of ischemic stroke. However, a high dose intravenous infusion is required to maintain effective drug concentration, owing to the short half-life of the thrombolytic drug, whereas a momentous limitation is the risk of bleeding. We envision a dual targeted strategy for rtPA delivery will be feasible to minimize the required dose of rtPA for treatment. For this purpose, rtPA and fibrin-avid peptide were co-immobilized to poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (PMNP) to prepare peptide/rtPA conjugated PMNPs (pPMNP-rtPA). During preparation, PMNP was first surface modified with avidin, which could interact with biotin. This is followed by binding PMNP-avidin with biotin-PEG-rtPA (or biotin-PEG-peptide), which was prepared beforehand by binding rtPA (or peptide) to biotin-PEG-maleimide while using click chemistry between maleimide and the single –SH group in rtPA (or peptide). The physicochemical property characterization indicated the successful preparation of the magnetic nanoparticles with full retention of rtPA fibrinolysis activity, while biological response studies underlined the high biocompatibility of all magnetic nanoparticles from cytotoxicity and hemolysis assays in vitro. The magnetic guidance and fibrin binding effects were also confirmed, which led to a higher thrombolysis rate in vitro using PMNP-rtPA or pPMNP-rtPA when compared to free rtPA after static or dynamic incubation with blood clots. Using pressure-dependent clot lysis model in a flow system, dual targeted pPMNP-rtPA could reduce the clot lysis time for reperfusion by 40% when compared to free rtPA at the same drug dosage. From in vivo targeted thrombolysis in a rat embolic model, pPMNP-rtPA was used at 20% of free rtPA dosage to restore the iliac blood flow in vascular thrombus that was created by injecting a blood clot to the hind limb area.

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Section: In Vitro Thrombolysismentioning

confidence: 99%

Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy

Chen

Hsu

et al. 2020

IJMS

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“…In this research, we call sol-gel alumina NPs as boehmite nanoparticles (NPs) in the reason of properties studying of nanoparticles that form stable alumina colloid. In our previous papers, we showed a promising approach to the creation of composite materials based on alumina and biomolecules by direct entrapment of the proteins within the sol-gel derived boehmite matrix (AlOOH) 25–27 . In this approach, the protein is immobilized in the xerogel boehmite cage during the room-temperature sol-gel transition 28,29 .…”

Section: Introductionmentioning

confidence: 99%

“…In this approach, the protein is immobilized in the xerogel boehmite cage during the room-temperature sol-gel transition 28,29 . It was shown, that it is possible to obtain systems both with complete immobilization of biomacromolecules and partial release of the proteins depending on the ratio of components and environmental conditions 26,27 . The entrapped proteins tightly interact with the walls of the ceramic matrix, which leads to an increase of their thermo- and photo-stability, so the structure of the immobilized protein can be preserved even at temperatures above the denaturation temperature under normal conditions 28–30 .…”

Section: Introductionmentioning

confidence: 99%

Sol-gel derived boehmite nanostructures is a versatile nanoplatform for biomedical applications

Solovev

Prilepskii

Krivoshapkina

et al. 2019

Sci Rep

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Alumina is one of the most promising carriers for drug delivery due to the long history of its usage as a vaccine adjuvant. Sol-gel synthesis provides excellent conditions for entrapment of biomolecules within an inorganic cage providing stabilization of proteins under the extremal conditions. In this paper, we show in vitro investigation of monodisperse alumina xerogel nanocontainers (AXNCs) using bovine serum albumin as a model protein entrapped in sol-gel alumina building blocks. Particularly, dose and cell-type dependent cytotoxicity in HeLa and A549 cancer cell lines were employed as well as investigation of antibacterial effect and stability of AXNCs in different biological media. It was shown, that the release of entrapped protein could be provided only in low pH buffer (as in cancer cell cytoplasm). This property could be applied for anticancer drug development. We also discovered boehmite nanoparticles effect on horizontal gene transfer and observed the appearance of antibiotic resistance by means of exchanging of the corresponding plasmid between two different E. coli strains. The present work may help to understand better the influence of AXNCs on various biological systems, such as prokaryotic and eukaryotic cells, and the activity of AXNCs in different biological media.

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“…The obtained results evidence that the use of hemostatic drugs is possible not only when applied to the exterior of the vessel, but also from the inside, performing the function of blood cells that can also participate in the cascade of blood-hemostasis reactions, while providing an external control. The overall strategy and the study of the new material are carried out in conjunction with the previously proposed approach to the development of new materials for minimally invasive surgery 18 , 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

Thrombin@Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding

Shabanova

Drozdov

Fakhardo

et al. 2018

Sci Rep

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Bleeding remains one of the main causes of premature mortality at present, with internal bleeding being the most dangerous case. In this paper, magnetic hemostatic nanoparticles are shown for the first time to assist in minimally invasive treatment of internal bleeding, implying the introduction directly into the circulatory system followed by localization in the bleeding zone due to the application of an external magnetic field. Nanoparticles were produced by entrapping human thrombin (THR) into a sol-gel derived magnetite matrix followed by grinding to sizes below 200 nm and subsequent colloidization. Prepared colloids show protrombotic activity and cause plasma coagulation in in vitro experiments. We also show here using a model blood vessel that the THR@ferria composite does not cause systematic thrombosis due to low activity, but being concentrated by an external magnetic field with simultaneous fibrinogen injection accelerates local hemostasis and stops the bleeding. For instance, a model vessel system with circulating blood at the puncture of the vessel wall and the application of a permanent magnetic field yielded a hemostasis time by a factor of 6.5 shorter than that observed for the control sample. Biocompatibility of composites was tested on HELF and HeLa cells and revealed no toxic effects.

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Streptokinase@alumina nanoparticles as a promising thrombolytic colloid with prolonged action

Abstract: A fully biocompatible thrombolytic nanocolloid providing high stability and prolonged activity has been developed.

Cited by 28 publications

References 30 publications

Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy

Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy

Sol-gel derived boehmite nanostructures is a versatile nanoplatform for biomedical applications

Thrombin@Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding

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