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聚乙二醇-聚(D,L-乳酸)纳米胶囊与宿主心肌细胞和感染性形式的克氏锥虫的体外相互作用。

In vitro interaction of polyethylene glycol-block-poly(D,L-lactide) nanocapsule devices with host cardiomyoblasts and Trypanosoma cruzi-infective forms.

机构信息

Laboratory of Pharmaceutics and Nanotechnology (LDGNano), School of Pharmacy, Federal University of Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.

Laboratory of Parasitic Diseases - NUPEB, Medical School, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.

出版信息

Parasitol Res. 2022 Oct;121(10):2861-2874. doi: 10.1007/s00436-022-07618-0. Epub 2022 Aug 16.

Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an important public health problem in Latin America. Nanoencapsulation of anti-T. cruzi drugs has significantly improved their efficacy and reduced cardiotoxicity. Thus, we investigated the in vitro interaction of polyethylene glycol-block-poly(D,L-lactide) nanocapsules (PEG-PLA) with trypomastigotes and with intracellular amastigotes of the Y strain in cardiomyoblasts, which are the infective forms of T. cruzi, using fluorescence and confocal microscopy. Fluorescently labeled nanocapsules (NCs) were internalized by non-infected H9c2 cells toward the perinuclear region. The NCs did not induce significant cytotoxicity in the H9c2 cells, even at the highest concentrations and interacted equally with infected and non-infected cells. In infected cardiomyocytes, NCs were distributed in the cytoplasm and located near intracellular amastigote forms. PEG-PLA NCs and trypomastigote form interactions also occurred. Altogether, this study contributes to the development of engineered polymeric nanocarriers as a platform to encapsulate drugs and to improve their uptake by different intra- and extracellular forms of T. cruzi, paving the way to find new therapeutic strategies to fight the causative agent of Chagas disease.

摘要

克氏锥虫引起的恰加斯病是拉丁美洲一个重要的公共卫生问题。抗克氏锥虫药物的纳米胶囊化显著提高了它们的疗效并降低了心脏毒性。因此,我们使用荧光和共聚焦显微镜研究了聚乙二醇-聚(D,L-乳酸)纳米囊(PEG-PLA)与锥虫的鞭毛体和心肌细胞内的 Y 株无鞭毛体的体外相互作用,心肌细胞是克氏锥虫的感染形式。荧光标记的纳米囊(NCs)被未感染的 H9c2 细胞向核周区域内化。即使在最高浓度下,NCs也不会在 H9c2 细胞中引起明显的细胞毒性,并且与感染和未感染的细胞同等相互作用。在感染的心肌细胞中,NCs分布在细胞质中,位于细胞内无鞭毛体形式附近。PEG-PLA NCs 与锥虫鞭毛体形式也发生相互作用。总之,这项研究为工程聚合纳米载体的开发做出了贡献,作为封装药物的平台,并提高它们被不同的细胞内和细胞外形式的克氏锥虫吸收的能力,为寻找治疗恰加斯病病原体的新治疗策略铺平了道路。

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