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一种新型可降解聚乙二醇超顺磁性氧化铁胶囊与多酚纳米酶缀合物(PSPM-NE)相结合,用于治疗由活性氧驱动的心血管疾病,以动脉粥样硬化作为模型疾病进行测试,并假设自身免疫是动脉粥样硬化的触发因素。

A novel degradable PEG superparamagnetic iron oxide capsule coupled with a polyphenolic nano-enzymatic conjugate (PSPM-NE), to treat ROS-driven cardiovascular-diseases, tested in atherosclerosis as a model disease, and hypothesizing autoimmunity as an atheroma's trigger.

作者信息

Pereira Glaucia C

机构信息

Department of Bioengineering, Faculty of Engineering, Imperial College London, London, United Kingdom.

出版信息

Front Cardiovasc Med. 2024 Jul 2;11:1125571. doi: 10.3389/fcvm.2024.1125571. eCollection 2024.

Abstract

Cardiovascular diseases account for a significant portion of the worldwide mortality rate. This aroused interest among the specialised scientific community, seeking for solutions based on non-clinical and clinical investigations, to shed light onto the physio-pathology of cardiovascular impairment. It is proven challenging managing chronic cardiovascular illnesses like atherosclerosis, arrhythmias, and diverse cardiomyopathies. In certain cases, there is no approved treatment. In other cases, the need for combining therapeutic components, when dealing with co-morbidities, may increase the risk of toxicity-driven cardiovascular impairment. In this case, because the risk of cardiac events correlates with the QT prolongation rates, the QT or QTc interval prolongation has become an important biomarker to access drug-related cardio-toxicity. Several approaches have been found in the current literature, aiming at improving physiological acceptance, i.e., to reduce toxicity. Nanotechnology has increasingly appeared as a promising ally to modulate active substances, preserving cardiovascular function and optimising drug effectiveness, i.e., acting as a cardio-protective mechanism, leveraging the effects of drug-driven cardio-toxicity. In this manuscript, the author combines plant active compounds and nanotechnological strategies, e.g., nano-encapsulation, nano-enzymes, magnetically driven nano-delivery systems, applied in regenerative medicine, and assesses their effects on the cardiovascular system, e.g., as cardio-protective factors, reducing cardio-toxicity. The aim is to propose a new strategy to tackle atherosclerosis initiation and progression, in a drug design that targets ROS-removal and reduces inflammation, using auto-immunity biomarkers to select key atheroma-related signalling cascades. To analyse physiological phenomena related to atherosclerosis initiation and progression, the author proposes both experimental observations and a new haemorheological computational model of arterial constriction. The results of such analysis are used as motivators in the design of the here presented strategy to tackle atheroma. This novel design is based on degradable polyethylene glycol (PEG) superparamagnetic iron oxide capsule coupled with a polyphenolic nano-enzymatic conjugate (PSPM-NE).

摘要

心血管疾病在全球死亡率中占很大比例。这引起了专业科学界的兴趣,他们通过非临床和临床研究寻求解决方案,以阐明心血管损伤的生理病理学。事实证明,管理诸如动脉粥样硬化、心律失常和各种心肌病等慢性心血管疾病具有挑战性。在某些情况下,没有获批的治疗方法。在其他情况下,处理合并症时需要联合治疗成分,这可能会增加由毒性引起的心血管损伤风险。在这种情况下,由于心脏事件的风险与QT间期延长率相关,QT或QTc间期延长已成为评估药物相关心脏毒性的重要生物标志物。目前的文献中已经发现了几种方法,旨在提高生理耐受性,即降低毒性。纳米技术越来越多地成为调节活性物质、保护心血管功能和优化药物有效性的有前景的辅助手段,即作为一种心脏保护机制,利用药物驱动的心脏毒性的影响。在本手稿中,作者将植物活性化合物与纳米技术策略相结合,例如纳米封装、纳米酶、磁驱动纳米递送系统,应用于再生医学,并评估它们对心血管系统的影响,例如作为心脏保护因子,降低心脏毒性。目的是提出一种新策略,以解决动脉粥样硬化的起始和进展问题,该药物设计针对清除活性氧并减轻炎症,使用自身免疫生物标志物来选择与动脉粥样硬化相关的关键信号级联。为了分析与动脉粥样硬化起始和进展相关的生理现象,作者提出了实验观察结果以及一种新的动脉收缩血液流变学计算模型。这种分析结果被用作设计此处提出的解决动脉粥样硬化策略的动力。这种新颖的设计基于可降解的聚乙二醇(PEG)超顺磁性氧化铁胶囊与多酚纳米酶缀合物(PSPM-NE)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11323396/bdc15fc0864c/fcvm-11-1125571-g001.jpg

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