一种对炎症微环境有反应的纳米疗法,用于动脉粥样硬化的双靶向治疗

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Ge Li PhD , Fei Xu PhD , Bo Yang MSc , Xinyue Lu MSc , Xiangyu Li PhD , Yanfei Qi PhD , Lesheng Teng PhD , Youxin Li PhD , Fengying Sun PhD , Wenhua Liu PhD
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引用次数: 4

摘要

动脉粥样硬化仍然是死亡和残疾的主要原因,也是冠状动脉疾病的主要原因。炎症是动脉硬化的致病因素之一;然而,目前基于降低动脉粥样硬化患者斑块组织炎症水平的治疗尚未临床应用。在此,我们假设αvβ3受体亲和性和低pH敏感性可能被认为是根据炎症微环境靶向动脉粥样硬化部位的有效治疗策略。为了证明这一初步假设,我们合成了一种酸不稳定的聚酮材料PK3,并利用cRGDfc肽修饰由聚丙交酯-乙醇酸酯(PLGA)、卵磷脂和PK3组成的纳米颗粒,装载抗动脉粥样硬化药物雷帕霉素(RAP)。采用O/W法制备了纳米颗粒,并对其进行了表征,结果表明纳米颗粒尺寸合适,具有良好的响应特性。体外释放研究和稳定性试验表明,这些纳米颗粒能被人脐静脉内皮细胞(HUVEC)有效内化,并表现出良好的体外抗炎作用。静脉注射后,ph反应性纳米疗法(RAP-Nps-RGD)靶向的RGD可能在ApoE−/−动脉粥样硬化小鼠的斑块部位积累,与其他制剂相比,可以有效地减缓斑块进展。此外,其良好的安全性和生物相容性已在体外和体内试验中得到证实。因此,纳米颗粒对炎症微环境的反应,通过炎症调节来预防动脉粥样硬化的前景,为将替代药物分子施用于炎症部位以减缓动脉硬化过程提供了巨大的可行性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A nanotherapy responsive to the inflammatory microenvironment for the dual-targeted treatment of atherosclerosis

Atherosclerosis remains the main cause of death and disability, as well as a leading cause of coronary arterial disease. Inflammation is one of the pathogenic factors of arteriosclerosis; however, the current treatments based on lowering the level of inflammation in the plaque tissue of patients with atherosclerosis are not clinically used. Herein, we hypothesize that αvβ3 receptor affinity and low pH sensitivity may be regarded as a valid therapeutic strategy for targeting sites of atherosclerosis according to the microenvironments of inflammation. To prove this tentative hypothesis, an acid-labile material polyketal named PK3 was synthesized, and the cRGDfc peptide was used to modify nanoparticles composed of poly(lactide-co-glycolide) (PLGA), lecithin, and PK3, loaded with the anti-atherosclerotic drug rapamycin (RAP). The nanoparticles were prepared using an O/W method and then characterized, which showed an appropriate particle size and fulfilling responsive behaviors. In vitro release studies and stability tests showed that these nanoparticles can be effectively internalized by human umbilical vein endothelial cells (HUVEC), and also show a good in vitro anti-inflammatory effect. After intravenous (i.v.) injection, RGD targeted by pH-responsive nanotherapy (RAP-Nps-RGD) may be accumulated at the plaque site in ApoE−/− mice with atherosclerosis and can effectively attenuate plaque progression compared to other formulations. Moreover, its good safety profile and biocompatibility have been revealed in both in vitro and in vivo estimations. Accordingly, the prospect of nanoparticles responsive to the inflammatory microenvironment for preventing atherosclerotic through inflammation modulation provides great feasibility for the administration of alternate drug molecules to inflamed sites to slow down the process of arteriosclerosis.

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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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