Intelligent antithrombotic nanomedicines: Progress, opportunities, and challenges

Xu, Junchao; Zhang, Yinlong; Nie, Guangjun

doi:10.1002/viw.20200145

Cited by 13 publications

(3 citation statements)

References 96 publications

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“…Different strategies have been evaluated, the most common approach is the coating with antithrombogenic molecules such as heparin and fibronectin. Other coatings include the use of anticoagulant peptides and nanoplatforms with antithrombogenic drugs ( Chen et al, 2019 ; Xu et al, 2021 ). One of the most successful strategies is the incorporation of polyethylene glycol (PEG) derivatives.…”

Section: Introductionmentioning

confidence: 99%

Redefining vascular repair: revealing cellular responses on PEUU—gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models

Rodríguez-Soto,

Riveros-Cortés,

Orjuela-Garzón

et al. 2024

Front. Bioeng. Biotechnol.

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Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Redefining vascular repair: revealing cellular responses on PEUU—gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models

Rodríguez-Soto,

Riveros-Cortés,

Orjuela-Garzón

et al. 2024

Front. Bioeng. Biotechnol.

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“…These drugs often have only limited effectiveness when they are used alone, for example, their penetration into clots tends to be trivial and requires larger doses. Making matters worse, they may also cause hemorrhagic transformation leading to fatal intracerebral hemorrhage, as well as some other undesirable side-effects ( Pfefferkorn and Rosenberg, 2003 ; Mao et al, 2017 ; Powers et al, 2018 ; Xu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Thrombus-Targeting Polymeric Nanocarriers and Their Biomedical Applications in Thrombolytic Therapy

Guan

Dou

2021

Front. Physiol.

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Due to the high morbidity and mortality of cardiovascular diseases, there is an urgent need for research on antithrombotic strategies. In view of the short half-life, insufficient drug penetration, poor targeting capabilities, and hemorrhagic side-effects of traditional thrombus treatment methods, the combination of thrombolytic therapy and nanocarriers brought by the development of nanotechnology in recent years may provide effective solutions for these undesirable side-effects caused by insufficient targeting. Polymeric nanocarriers, based on macromolecules and various functional groups, can connect specific targeting molecules together through chemical modification to achieve the protection and targeted delivery of thrombolytic drugs. However, simple chemical molecular modifications may be easily affected by the physiological environment encountered in the circulatory system. Therefore, the modification of nanocarriers with cell membranes can provide camouflage to these platforms and help to extend their circulation time while also imparting them with the biological functions of cell membranes, thus providing them with precise targeting capabilities, among which the most important is the biological modification of platelet membranes. In addition, some nanoparticles with their own therapeutic functions have also been developed, such as polypyrrole, which can exhibit a photothermal effect to induce thrombolysis. Herein, combined with the mechanism of thrombosis and thrombolysis, we outline the recent advances achieved with thrombus-targeting nanocarriers with regard to thrombosis treatment. On this basis, the design considerations, advantages, and challenges of these thrombolytic therapies in clinical transformation are discussed.

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“… 1 , 2 Due to the dominant role of activated platelets in the formation of pathological thrombosis, controllable platelet inhibition is regarded as a central strategy against thrombogenesis. 3 To date, the clinical usage of antiplatelet agents (APAs), mainly aspirin, P2Y 12 inhibitors (eg, clopidogrel, ticagrelor, cangrelor, and prasugrel), GP (glycoprotein) IIb/IIIa inhibitors (eg, tirofiban, eptifibatide, and abciximab), and PAR (protease-activated receptor) inhibitors, has become one of the main strategies in the treatment of thrombosis-associated diseases. 4 During the medication period, life-threatening bleeding events, in particular intracranial hemorrhage, stand a fair chance of occurrence.…”

mentioning

confidence: 99%

Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents

Yan

Gao

et al. 2023

Circulation Research

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During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs. Although platelet transfusion has become a common practice to counteract the function of APAs, personalized dosage of platelet transfusion is difficult to be judged by assessing the trade-off between its effectiveness and additional thrombotic risk. Here we reported a platelet-mimicking perfluorocarbon-based nanosponge, which potently reversed the antiplatelet effect of APAs by competitively binding with APAs. Platelet-mimicking perfluorocarbon-based nanosponges showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis. In summary, our results demonstrated the safety and effectiveness of the platelet-mimicking nanosponge in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

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Intelligent antithrombotic nanomedicines: Progress, opportunities, and challenges

Cited by 13 publications

References 96 publications

Redefining vascular repair: revealing cellular responses on PEUU—gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models

Redefining vascular repair: revealing cellular responses on PEUU—gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models

Thrombus-Targeting Polymeric Nanocarriers and Their Biomedical Applications in Thrombolytic Therapy

Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents

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