Hyperthermia-triggered UK release nanovectors for deep venous thrombosis therapy

Xu, Jiasheng; Zhou, Yu; Xiong, Zhiwei; Ouyang, Huan; Huang, Li; Fang, Huaqiang; Jiang, Huixia; Huang, Feng; Yao, Yang; Ding, Xingwei; Wang, Xiaolei; Zhou, Weimin

doi:10.1039/c9tb01851d

Cited by 16 publications

(14 citation statements)

References 20 publications

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“…Wang and coworkers developed another strategy for NIR‐mediated thrombolysis combining gold nanoparticles and light‐activated uPA release. [ 13,115,117 ] Initially, uPA‐loaded gold mesoporous silica core–shell nanospheres were developed and capped with thermosensitive tetradecanol and tested for on‐demand release of uPA upon NIR irradiation (808 nm, 5 W cm −2 ). Enhanced bleeding free‐fibrinolysis was achieved in murine tail‐thrombus model through synergistic photothermal–biochemical thrombolysis effect of gold and uPA, respectively.…”

Section: Stimuli‐mediated Thrombolysismentioning

confidence: 99%

“…[ 112,113 ] NIR‐mediated photothermal thrombolysis has recently emerged as a new strategy for thrombus disintegration using gold nanostructures based on their surface plasmon resonance properties which enable them to convert light into local hyperthermia. [ 13,16,114–117 ] Dual‐photothermal/photodynamic thrombolysis has also been reported using nanostructured porphyrin. [ 118 ]…”

Section: Stimuli‐mediated Thrombolysismentioning

confidence: 99%

“…Other strategies have addressed this drawback combining photothermal ablation with thrombolytic agents or photodynamic therapy. [ 115,116,118 ] A NIR‐driven biocompatible micromotor system was fabricated by Shao et al. [ 116 ] through layer‐by‐layer assembly of chitosan and heparin followed by partial coating of the formed microcapsules with gold shells.…”

Section: Stimuli‐mediated Thrombolysismentioning

confidence: 99%

See 2 more Smart Citations

Smart Delivery of Plasminogen Activators for Efficient Thrombolysis; Recent Trends and Future Perspectives

Refaat

Rosal

Palasubramaniam

et al. 2021

Advanced Therapeutics

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Fibrinolytic drugs have been successfully used to manage acute thrombotic and thromboembolic conditions. However, their narrow administration time window, rapid clearance, and possible inactivation limit their efficient and wider application. Most importantly, they present a substantial risk of fatal bleeding complications, which are a major cause of mortality and morbidity. Improving the therapeutic outcomes of pharmacological thrombolysis, including alleviating associated side effects, is an urgent challenge. In this context, nano‐drug delivery systems have attracted major interest. State‐of‐the‐art nanodelivery systems have achieved reduced immunogenicity and a significant prolongation of the biological half‐life of drugs, the latter allowing their application as boli instead of infusions. Recent research focuses on theranostic systems capable of image‐guided thrombolysis, clot targeting strategies, and stimuli‐responsive systems. The latter are designed so that an external or internal stimulus triggers the drug release, offering unique spatiotemporal control over the treatment and potentially minimizing side effects. In this review, the authors discuss the different nanodelivery platforms and focus on stimuli‐responsive systems, highlighting their therapeutic advantages and the challenges for their clinical translation.

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Section: Stimuli‐mediated Thrombolysismentioning

confidence: 99%

Section: Stimuli‐mediated Thrombolysismentioning

confidence: 99%

Section: Stimuli‐mediated Thrombolysismentioning

confidence: 99%

See 1 more Smart Citation

Smart Delivery of Plasminogen Activators for Efficient Thrombolysis; Recent Trends and Future Perspectives

Refaat

Rosal

Palasubramaniam

et al. 2021

Advanced Therapeutics

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“…Through thermal thrombolysis, the Au-MSN provides a more secure protocol for TA delivery through high efficiency and drug secretion. [95] In another study, Zhou et al [96] delivered the UK to the deep vein thrombosis of the lower extremities using mesoporous silica/gold shell-core nanostructures (Au@MSNs). The eutectic mixture of fatty acids (stearic acid and lauric acid) was applied to the Au@MSNs pores for hyperthermia-triggered UK release.…”

Section: Gold Nps (Au Nps)mentioning

confidence: 99%

“…In addition to the rapid drug release, thrombolytic effect was further enhanced by local hyperthermia. [96]…”

Section: Gold Nps (Au Nps)mentioning

confidence: 99%

Thrombolytic Agents: Nanocarriers in Controlled Release

Hassanpour

Kim

Saadati

et al. 2020

Small

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Thrombosis is a life-threatening pathological condition in which blood clots form in blood vessels, obstructing or interfering with blood flow. Thrombolytic agents (TAs) are enzymes that can catalyze the conversion of plasminogen to plasmin to dissolve blood clots. The plasmin formed by TAs breaks down fibrin clots into soluble fibrin that finally dissolves thrombi. Several TAs have been developed to treat various thromboembolic diseases, such as pulmonary embolisms, acute myocardial infarction, deep vein thrombosis, and extensive coronary emboli. However, systemic TA administration can trigger non-specific activation that can increase the incidence of bleeding. Moreover, protein-based TAs are rapidly inactivated upon injection resulting in the need for large doses. To overcome these limitations, various types of nanocarriers have been introduced that enhance the pharmacokinetic effects by protecting the TA from the biological environment and targeting the release into coagulation. The nanocarriers show increasing half-life, reducing side effects, and improving overall TA efficacy. In this work, the recent advances in various types of TAs and nanocarriers are thoroughly reviewed. Various types of nanocarriers, including lipid-based, polymer-based, and metal-based nanoparticles are described, for the targeted delivery of TAs. This work also provides insights into issues related to the future of TA development and successful clinical translation.

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Activated Platelet‐Targeted IR780 Immunoliposomes for Photothermal Thrombolysis

Refaat

Rosal

Bongcaron

et al. 2022

Adv Funct Materials

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Acute thrombosis is a leading cause of mortality and morbidity worldwide. Pharmacological thrombolysis relies on plasminogen activators (PAs), which are associated with major side effects including potentially fatal bleeding. Alternative therapeutic options that do not rely on PAs are urgently required. Here, the efficacy of targeted photothermal therapy is evaluated for thrombolysis using liposomes loaded with IR780 dye, which release heat upon near‐infrared (NIR) irradiation. Liposomes targeted to activated platelets—one of the main components of thrombi—accumulate preferentially in thrombi both in vitro and in vivo compared to non‐targeted controls. In a mouse model of thrombosis, targeted IR780 immunoliposomes (Tar‐IR‐L) produce ≈12 °C average local temperature increase upon NIR irradiation (5 min, 1 W cm−2). This causes a significant reduction in clot area compared to controls treated with non‐targeted liposomes or phosphate‐buffered saline, which only increase local temperature slightly (6 and 3 °C) when irradiated. Co‐loading a low‐dose single chain urokinase plasminogen activator (scuPA) to targeted IR780 liposomes (Tar‐scuPA‐IR‐L) does not result in a superior thrombolytic effect, which indicates that photothermal therapy alone may allow thrombolysis without the need for fibrinolytic drugs. This approach may prevent potential bleeding complications, promising a safer alternative to current pharmacological approaches.

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Hyperthermia-triggered UK release nanovectors for deep venous thrombosis therapy

Abstract: Deep vein thrombosis (DVT) is a common and lethal complication of surgery.

Cited by 16 publications

References 20 publications

Smart Delivery of Plasminogen Activators for Efficient Thrombolysis; Recent Trends and Future Perspectives

Smart Delivery of Plasminogen Activators for Efficient Thrombolysis; Recent Trends and Future Perspectives

Thrombolytic Agents: Nanocarriers in Controlled Release

Activated Platelet‐Targeted IR780 Immunoliposomes for Photothermal Thrombolysis

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