LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques.
LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques.
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DOI：
10.1016/j.bioactmat.2022.02.022
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发表时间：
2022-10
影响因子：
18.9
通讯作者：
Guo D
中科院分区：
文献类型：
--
作者：
Hou J;Zhou J;Chang M;Bao G;Xu J;Ye M;Zhong Y;Liu S;Wang J;Zhang W;Ran H;Wang Z;Chen Y;Guo D
易损的动脉粥样硬化斑块由于撕裂和破裂的风险很高，会导致严重的心脑血管疾病。尽管现有的临床方法可以评估斑块的易损性，并在心血管事件发生前对易损斑块进行特异的治疗，但效率仍然较低，不可取。在这里，我们合理地设计和设计了低强度聚焦超声(LIFU)响应型FPD@CD纳米药物，通过轻松地将相变剂全氟己烷(PFH)负载到生物相容的PLGA-PEG-PLGA纳米粒子(PPP NPs)中，然后将葡聚糖硫酸盐(DS)附着在PPP NPs的表面进行靶向递送，从而高效地治疗易损斑块。DS作为一种典型的巨噬细胞靶向分子，可以实现NPs的精确汽化，进而通过声学液滴汽化效应诱导RAW 264.7巨噬细胞的可控凋亡。此外，DIR和Fe3O4的引入赋予纳米医学近红外荧光(NIRF)和磁共振(MR)成像能力。基于体内和体外评估结果，以巨噬细胞为治疗靶点的工程FPD@CD纳米药物达到了缩小易损斑块的显著治疗效果。在整个治疗期间，大体病理标本的血管狭窄程度降低了49.4%。这种特殊、高效和生物安全的治疗方式在缓解斑块破裂担忧的基础上，增强了生物医学在心脑血管疾病患者中的应用。一种新的纳米药物使能的治疗策略已经开发出来，通过使用ADV来治疗脆弱的斑块。探索了治疗ADV的最佳治疗条件，包括利福照射功率强度和斑块稳定性。系统地研究了纳米药物激活的ADV治疗易损斑块的潜在机制。
Due to the high risk of tearing and rupture, vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases. Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event, but the efficiency is still low and undesirable. Herein, we rationally design and engineer the low-intensity focused ultrasound (LIFU)-responsive FPD@CD nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane (PFH) into biocompatible PLGA-PEG-PLGA nanoparticles (PPP NPs) and then attaching dextran sulphate (DS) onto the surface of PPP NPs for targeting delivery. DS, as a typical macrophages-targeted molecule, can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization (ADV) effect. In addition, the introduction of DiR and Fe3O4 endows nanomedicine with near-infrared fluorescence (NIRF) and magnetic resonance (MR) imaging capabilities. The engineered FPD@CD nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes. A reduction of 49.4% of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period. This specific, efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns. A new nanomedicine-enabled treatment strategy has been developed for treating vulnerable plaques by employing ADV. The optimal treatment conditions for ADV have been explored, including LIFU irradiation power intensity and plaque stability. The underlying mechanism of nanomedicine-enabled ADV in the treatment of vulnerable plaques has been studied systematically.
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影响因子：
10.2
作者：
Chen X;Zhang Y;Zhang H;Zhang L;Liu L;Cao Y;Ran H;Tian J
通讯作者：
Tian J
用于无创缓解动脉粥样硬化斑块进展的模拟血小板治疗系统
DOI：
10.1002/advs.202004128
发表时间：
2021-04
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Ma Y;Ma Y;Gao M;Han Z;Jiang W;Gu Y;Liu Y
通讯作者：
Liu Y
DOI：
10.1177/1074248418778836
发表时间：
2018-11-01
影响因子：
2.6
作者：
Gomes, Fernando L. T.;Maranhao, Raul C.;Serrano, Carlos V., Jr.
通讯作者：
Serrano, Carlos V., Jr.
影响因子：
4.6
作者：
Calatayud MP;Soler E;Torres TE;Campos-Gonzalez E;Junquera C;Ibarra MR;Goya GF
通讯作者：
Goya GF
影响因子：
16.6
作者：
Duivenvoorden R;Tang J;Cormode DP;Mieszawska AJ;Izquierdo-Garcia D;Ozcan C;Otten MJ;Zaidi N;Lobatto ME;van Rijs SM;Priem B;Kuan EL;Martel C;Hewing B;Sager H;Nahrendorf M;Randolph GJ;Stroes ES;Fuster V;Fisher EA;Fayad ZA;Mulder WJ
通讯作者：
Mulder WJ