Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle

Chen, Jyh‐Ping; Yang, Pei-Ching; Ma, Yunn‐Hwa; Tu, Shu-Ju; Lu, Yu-Jen

doi:10.2147/ijn.s36197

Cited by 76 publications

(57 citation statements)

References 60 publications

(51 reference statements)

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“…Magnetic therapeutic agents are an area of active research, and numerous particles have been developed that are tailored for different uses (7,8,10,15,17–21). Magnetic manipulation of iron particles has been performed in the setting of IAC to help localize particles with an external magnet and also with alternating magnetic fields to create local hyperthermia in tumors (ie, magnetic fluid hyperthermia) and augment thrombolysis (7–10,14–16,19,20,22–25). The concept proposed here is to use magnetism for the purposes of intravascular filtration.…”

Section: Discussionmentioning

confidence: 99%

“…MTC-DOX was estimated to release 25% of the bound drug into human plasma over a period of 3 hours, but numerous different types of magnetic iron oxide particles have been bound to doxorubicin, with different affinities, stabilities, sizes, and behaviors in various microenvironments depending on the characteristics of the particles (7,8,10,15,17,18). Other agents and classes of medications, including thrombolytic agents, have also been bound to iron oxide particles and could potentially also be used with the technology developed in this investigation (7,8,19–21). …”

mentioning

confidence: 99%

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In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study

Mabray¹,

Lillaney²,

Sze³

et al. 2016

Journal of Vascular and Interventional Radiology

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Purpose To establish that a magnetic device designed for intravascular use can bind small iron particles in physiologic flow models. Materials and Methods Uncoated iron oxide particles 50–100 nm and 1–5 μm in size were tested in a water flow chamber over a period of 10 minutes without a magnet (ie, control) and with large and small prototype magnets. These same particles and 1-μm carboxylic acid–coated iron oxide beads were likewise tested in a serum flow chamber model without a magnet (ie, control) and with the small prototype magnet. Results Particles were successfully captured from solution. Particle concentrations in solution decreased in all experiments (P < .05 vs matched control runs). At 10 minutes, concentrations were 98% (50–100-nm particles in water with a large magnet), 97% (50–100-nm particles in water with a small magnet), 99% (1–5-μm particles in water with a large magnet), 99% (1–5-μm particles in water with a small magnet), 95% (50–100-nm particles in serum with a small magnet), 92% (1–5-μm particles in serum with a small magnet), and 75% (1-μm coated beads in serum with a small magnet) lower compared with matched control runs. Conclusions This study demonstrates the concept of magnetic capture of small iron oxide particles in physiologic flow models by using a small wire-mounted magnetic filter designed for intravascular use.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study

Mabray¹,

Lillaney²,

Sze³

et al. 2016

Journal of Vascular and Interventional Radiology

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“…Other coating molecules such as carboxymethyl dextran 42 , silica 43 , poly [aniline-co-N-(1-one-butyric acid) aniline] 44 , and chitosan 45 were also utilized to decorate tPA-loaded MNP, and tPA was conjugated on the particle surface with either -COOH or -NH 2 functional groups. The resulted tPA-loaded MNP showed enhanced storage stability and almost full retention of thrombolytic activity.…”

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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“…As in other fibrinolytic particles discussed previously, encapsulating or immobilizing PA on MNP increases enzyme stability during storage and improves half‐life . Magnetic nanoparticles carrying tPA, uPA, or SK have been decorated with coatings that further improve half‐life and reduce immunogenicity including dextran, chitosan, silica, hydrosol, PLGA and PLA‐PEG, polyacrylic acid (PAA), PEG, poly[aniline‐co‐N‐(1‐one‐butyric acid) aniline], and heparin . Plasminogen activator functionalization of MNP can rely on either physical adsorption to the MNP matrix or covalent attachment .…”

Section: Magnetic Particles and Magnetic Field Controlmentioning

confidence: 99%

Engineered microparticles and nanoparticles for fibrinolysis

Disharoon

Marr

Neeves

2019

Journal of Thrombosis and Haemostasis

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Fibrinolytic agents including plasmin and plasminogen activators improve outcomes in acute ischemic stroke and thrombosis by recanalizing occluded vessels. In the decades since their introduction into clinical practice, several limitations of have been identified in terms of both efficacy and bleeding risk associated with these agents. Engineered nanoparticles and microparticles address some of these limitations by improving circulation time, reducing inhibition and degradation in circulation, accelerating recanalization, improving targeting to thrombotic occlusions, and reducing off‐target effects; however, many particle‐based approaches have only been used in preclinical studies to date. This review covers four advances in coupling fibrinolytic agents with engineered particles: (a) modifications of plasminogen activators with macromolecules, (b) encapsulation of plasminogen activators and plasmin in polymer and liposomal particles, (c) triggered release of encapsulated fibrinolytic agents and mechanical disruption of clots with ultrasound, and (d) enhancing targeting with magnetic particles and magnetic fields. Technical challenges for the translation of these approaches to the clinic are discussed.

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Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle

Cited by 76 publications

References 60 publications

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study

Tissue plasminogen activator-based nanothrombolysis for ischemic stroke

Engineered microparticles and nanoparticles for fibrinolysis

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