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基于 CaCO 的右旋糖酐/聚 L-精氨酸多层纳米系统用于血管内药物输送。

Dextran/poly-L-arginine multi-layered CaCO-based nanosystem for vascular drug delivery.

机构信息

Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy.

Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy.

出版信息

Int J Biol Macromol. 2021 Apr 30;177:548-558. doi: 10.1016/j.ijbiomac.2021.02.058. Epub 2021 Feb 9.

DOI:10.1016/j.ijbiomac.2021.02.058
PMID:33577822
Abstract

The development of heterogeneous drug delivery systems leads to innovative strategies for targeted therapy of common pathologies, such as cancer, immunological and neurological disorders. Nowadays, it is possible to choose among a great variety of nanoparticles on the basis of the needs they have to satisfy. However, a candidate for the treatment of cardiovascular pathologies is still missing. In this context, a targeted therapy implies the conceptualization of nanoparticles that take active part in the treatment of vascular pathologies. The aim of this work was to provide a method to produce multi-layered calcium carbonate (CaCO) nanoparticles encapsulating a model protein, bovine serum albumin, with model antibodies on their surface. CaCO nanoparticles were produced by the combination of complex coacervation and mineralization and were engineered using layer-by-layer technique with a polysaccharide, dextran sulfate, and a homo-poly-amino acid, poly-L-arginine. Morphology, biocompatibility, cellular uptake, influence on cell expression of the inflammatory marker matrix metalloproteinase-9, and hemocompatibility of the nanoparticles were studied. The presence of the dextran/poly-L-arginine layers did not negatively affect the nanoparticle overall characteristics and they did not trigger proinflammatory response in vitro. Taking together all the obtained results, we consider the proposed CaCO nanoparticles as a promising tool in cardiovascular field.

摘要

多相药物输送系统的发展为癌症、免疫和神经紊乱等常见疾病的靶向治疗带来了创新策略。如今,可以根据需要选择各种纳米粒子。然而,治疗心血管疾病的候选药物仍然缺失。在这种情况下,靶向治疗意味着需要设计能够积极参与治疗血管疾病的纳米粒子。本工作旨在提供一种生产多层碳酸钙(CaCO)纳米粒子的方法,该纳米粒子包封了一种模型蛋白,牛血清白蛋白,并在其表面带有模型抗体。CaCO 纳米粒子通过复凝聚和矿化相结合的方法制备,并通过层层技术用多糖葡聚糖硫酸酯和同聚多氨基酸聚精氨酸进行修饰。研究了纳米粒子的形态、生物相容性、细胞摄取、对炎症标志物基质金属蛋白酶-9表达的影响以及纳米粒子的血液相容性。葡聚糖/聚精氨酸层的存在并未对纳米粒子的整体特性产生负面影响,并且在体外也没有引发炎症反应。综合所有获得的结果,我们认为所提出的 CaCO 纳米粒子有望成为心血管领域的一种有前途的工具。

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