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杂化树状聚合物在体外对正常和癌细胞神经元的代际效应和进入线粒体的作用。

Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro.

机构信息

Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland.

Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain.

出版信息

Biomolecules. 2020 Mar 9;10(3):427. doi: 10.3390/biom10030427.

DOI:10.3390/biom10030427
PMID:32182909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7175207/
Abstract

Dendrimers as drug carriers can be utilized for drugs and siRNA delivery in central nervous system (CNS) disorders, including various types of cancers, such as neuroblastomas and gliomas. They have also been considered as drugs per se, for example as anti-Alzheimer's disease (AD), anti-cancer, anti-prion or anti-inflammatory agents. Since the influence of carbosilane-viologen-phosphorus dendrimers (SMT1 and SMT2) on the basic cellular processes of nerve cells had not been investigated, we examined the impact of two generations of these hybrid macromolecules on two murine cell lines-cancer cell line N2a (mouse neuroblastoma) and normal immortalized cell line mHippoE-18 (embryonic mouse hippocampal cell line). We examined alterations in cellular responses including the activity of mitochondrial dehydrogenases, the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, and morphological modifications and fractions of apoptotic and dead cells. Our results show that both dendrimers at low concentrations affected the cancer cell line more than the normal one. Also, generation-dependent effects were found: the highest generation induced greater cytotoxic effects and morphological modifications. The most promising is that the changes in mitochondrial membrane potential and transmission electron microscopy (TEM) images indicate that dendrimer SMT1 can reach mitochondria. Thus, SMT1 and SMT2 seem to have potential as nanocarriers to mitochondria or anti-cancer drugs per se in CNS disorders.

摘要

树枝状聚合物作为药物载体可用于治疗中枢神经系统(CNS)疾病中的药物和 siRNA 传递,包括各种类型的癌症,如神经母细胞瘤和神经胶质瘤。它们也被认为是本身就是药物,例如抗阿尔茨海默病(AD)、抗癌、抗朊病毒或抗炎药物。由于碳硅烷-紫精-磷树枝状聚合物(SMT1 和 SMT2)对神经细胞基本细胞过程的影响尚未被研究,我们研究了两代这些杂化大分子对两种鼠细胞系-癌细胞系 N2a(鼠神经母细胞瘤)和正常永生化细胞系 mHippoE-18(胚胎鼠海马细胞系)的影响。我们检查了细胞反应的变化,包括线粒体脱氢酶的活性、活性氧(ROS)的产生、线粒体膜电位的变化以及形态修饰和凋亡和死亡细胞的分数。我们的结果表明,两种树枝状聚合物在低浓度下对癌细胞系的影响大于正常细胞系。此外,还发现了代际依赖性效应:最高代际诱导更大的细胞毒性作用和形态修饰。最有希望的是,线粒体膜电位的变化和透射电子显微镜(TEM)图像表明,树枝状聚合物 SMT1 可以到达线粒体。因此,SMT1 和 SMT2 似乎有可能作为纳米载体用于 CNS 疾病中的线粒体或抗癌药物本身。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/b4ae3c31a183/biomolecules-10-00427-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/37d2f1e46e5a/biomolecules-10-00427-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/c6a986ef6932/biomolecules-10-00427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/4738109a10d0/biomolecules-10-00427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/dcd2921d7b8c/biomolecules-10-00427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/27c33501831b/biomolecules-10-00427-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/1e1b7159c986/biomolecules-10-00427-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/2e16fd9382e5/biomolecules-10-00427-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/7fa0d5192b86/biomolecules-10-00427-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/52055b2f95dd/biomolecules-10-00427-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/b4ae3c31a183/biomolecules-10-00427-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/37d2f1e46e5a/biomolecules-10-00427-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/c6a986ef6932/biomolecules-10-00427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/4738109a10d0/biomolecules-10-00427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/dcd2921d7b8c/biomolecules-10-00427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/27c33501831b/biomolecules-10-00427-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/1e1b7159c986/biomolecules-10-00427-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/2e16fd9382e5/biomolecules-10-00427-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/7fa0d5192b86/biomolecules-10-00427-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/52055b2f95dd/biomolecules-10-00427-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5409/7175207/b4ae3c31a183/biomolecules-10-00427-g010.jpg

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