Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro
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-can...
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MDPI AG
2020-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/3/427 |
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| author | Aleksandra Szwed Katarzyna Miłowska Sylwia Michlewska Silvia Moreno Dzmitry Shcharbin Rafael Gomez-Ramirez Francisco Javier de la Mata Jean-Pierre Majoral Maria Bryszewska Teresa Gabryelak |
| author_facet | Aleksandra Szwed Katarzyna Miłowska Sylwia Michlewska Silvia Moreno Dzmitry Shcharbin Rafael Gomez-Ramirez Francisco Javier de la Mata Jean-Pierre Majoral Maria Bryszewska Teresa Gabryelak |
| author_sort | Aleksandra Szwed |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:08:06Z |
| format | Article |
| id | doaj.art-3c3be972b7fa45aaa7c0e49899dc609e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-12T06:08:06Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-3c3be972b7fa45aaa7c0e49899dc609e2022-12-22T03:44:47ZengMDPI AGBiomolecules2218-273X2020-03-0110342710.3390/biom10030427biom10030427Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In VitroAleksandra Szwed0Katarzyna Miłowska1Sylwia Michlewska2Silvia Moreno3Dzmitry Shcharbin4Rafael Gomez-Ramirez5Francisco Javier de la Mata6Jean-Pierre Majoral7Maria Bryszewska8Teresa Gabryelak9Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, PolandDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, PolandDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, PolandDepartamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, SpainInstitute of Biophysics and Cell Engineering of NASB, Akademicheskaja, 27, Minsk 220072, BelarusDepartamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, SpainDepartamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, SpainLaboratoire de Chimie de Coordinations du CNRS, 205 route de Narbonne, BP 44099, Toulouse Cedex4, FranceDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, PolandDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, PolandDendrimers 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.https://www.mdpi.com/2218-273X/10/3/427apoptosiscytotoxicityn2amhippoe-18rosδψmtemcarbosilane–viologen–phosphorus dendrimers |
| spellingShingle | Aleksandra Szwed Katarzyna Miłowska Sylwia Michlewska Silvia Moreno Dzmitry Shcharbin Rafael Gomez-Ramirez Francisco Javier de la Mata Jean-Pierre Majoral Maria Bryszewska Teresa Gabryelak Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro Biomolecules apoptosis cytotoxicity n2a mhippoe-18 ros δψm tem carbosilane–viologen–phosphorus dendrimers |
| title | Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro |
| title_full | Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro |
| title_fullStr | Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro |
| title_full_unstemmed | Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro |
| title_short | Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro |
| title_sort | generation dependent effects and entrance to mitochondria of hybrid dendrimers on normal and cancer neuronal cells in vitro |
| topic | apoptosis cytotoxicity n2a mhippoe-18 ros δψm tem carbosilane–viologen–phosphorus dendrimers |
| url | https://www.mdpi.com/2218-273X/10/3/427 |
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