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search.filters.applied.f.access: openAccess × Author: Luo, Rifang × End date: 2024 × Start date: 2020 × DDC: 500 × Type: Text × Version: publishedVersion ×

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    A thrombin-triggered self-regulating anticoagulant strategy combined with anti-inflammatory capacity for blood-contacting implants
    (Washington, DC [u.a.] : Assoc., 2022) Wang, Yanan; Wu, Haoshuang; Zhou, Zhongyi; Maitz, Manfred F.; Liu, Kunpeng; Zhang, Bo; Yang, Li; Luo, Rifang; Wang, Yunbing
    Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the longterm function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings.
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    Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy
    ([Beijing] : China Association for Science and Technology, 2022) Chen, Liang; Zhou, Zhongyi; Hu, Cheng; Maitz, Manfred F.; Yang, Li; Luo, Rifang; Wang, Yunbing
    Atherosclerosis, the principle cause of cardiovascular disease (CVD) worldwide, is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Atherogenesis is associated with the upregulation of CD47, a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or "efferocytosis." Here, we have developed platelet membrane-coated mesoporous silicon nanoparticles (PMSN) as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody. Briefly, the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an affinity to plaques and atherosclerotic sites. The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47. In an atherosclerosis model established in ApoE-/- mice, PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques. Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis. Overall, this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy, which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis.