Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity
The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylAmino)(Phenyl) Phosphonium halides (AP...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/2079-4991/13/21/2840 |
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| author | Vladimir F. Mironov Mudaris N. Dimukhametov Andrey V. Nemtarev Tatiana N. Pashirova Olga V. Tsepaeva Alexandra D. Voloshina Alexandra B. Vyshtakalyuk Igor A. Litvinov Anna P. Lyubina Anastasiia S. Sapunova Dinara F. Abramova Vladimir V. Zobov |
| author_facet | Vladimir F. Mironov Mudaris N. Dimukhametov Andrey V. Nemtarev Tatiana N. Pashirova Olga V. Tsepaeva Alexandra D. Voloshina Alexandra B. Vyshtakalyuk Igor A. Litvinov Anna P. Lyubina Anastasiia S. Sapunova Dinara F. Abramova Vladimir V. Zobov |
| author_sort | Vladimir F. Mironov |
| collection | DOAJ |
| description | The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylAmino)(Phenyl) Phosphonium halides (APPs) containing one, two, or three diethylamino groups was obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions (20 °C) and high yields (93–98%). The structure of APP was established by NMR and XRD. A high in vitro cytotoxicity of APPs against M-HeLa, HuTu 80, PC3, DU-145, PANC-1, and MCF-7 lines was found. The selectivity index is in the range of 0.06–4.0 μM (SI 17-277) for the most active APPs. The effect of APPs on cancer cells is characterized by hyperproduction of ROS and depolarization of the mitochondrial membrane. APPs induce apoptosis, proceeding along the mitochondrial pathway. Incorporation of APPs into lipid systems (liposomes and solid lipid nanoparticles) improves cytotoxicity toward tumor cells and decrease toxicity against normal cell lines. The IC<sub>50</sub>s of lipid systems are lower than for the reference drug DOX, with a high SI (30–56) toward MCF-7 and DU-145. APPs exhibit high selective activity against Gram-positive bacteria <i>S. aureus 209P</i> and <i>B. segeus 8035</i>, including methicillin-resistant <i>S. aureus</i> (<i>MRSA-1, MRSA-2</i>), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead APP. |
| first_indexed | 2024-03-11T11:24:22Z |
| format | Article |
| id | doaj.art-755a68d9d32543f8992b408014263a30 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-11T11:24:22Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-755a68d9d32543f8992b408014263a302023-11-10T15:09:08ZengMDPI AGNanomaterials2079-49912023-10-011321284010.3390/nano13212840Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and ToxicityVladimir F. Mironov0Mudaris N. Dimukhametov1Andrey V. Nemtarev2Tatiana N. Pashirova3Olga V. Tsepaeva4Alexandra D. Voloshina5Alexandra B. Vyshtakalyuk6Igor A. Litvinov7Anna P. Lyubina8Anastasiia S. Sapunova9Dinara F. Abramova10Vladimir V. Zobov11Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, RussiaThe creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylAmino)(Phenyl) Phosphonium halides (APPs) containing one, two, or three diethylamino groups was obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions (20 °C) and high yields (93–98%). The structure of APP was established by NMR and XRD. A high in vitro cytotoxicity of APPs against M-HeLa, HuTu 80, PC3, DU-145, PANC-1, and MCF-7 lines was found. The selectivity index is in the range of 0.06–4.0 μM (SI 17-277) for the most active APPs. The effect of APPs on cancer cells is characterized by hyperproduction of ROS and depolarization of the mitochondrial membrane. APPs induce apoptosis, proceeding along the mitochondrial pathway. Incorporation of APPs into lipid systems (liposomes and solid lipid nanoparticles) improves cytotoxicity toward tumor cells and decrease toxicity against normal cell lines. The IC<sub>50</sub>s of lipid systems are lower than for the reference drug DOX, with a high SI (30–56) toward MCF-7 and DU-145. APPs exhibit high selective activity against Gram-positive bacteria <i>S. aureus 209P</i> and <i>B. segeus 8035</i>, including methicillin-resistant <i>S. aureus</i> (<i>MRSA-1, MRSA-2</i>), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead APP.https://www.mdpi.com/2079-4991/13/21/2840aminophosphonium saltliposomesolid lipid nanoparticleanticancer activityapoptosisantimicrobial activity |
| spellingShingle | Vladimir F. Mironov Mudaris N. Dimukhametov Andrey V. Nemtarev Tatiana N. Pashirova Olga V. Tsepaeva Alexandra D. Voloshina Alexandra B. Vyshtakalyuk Igor A. Litvinov Anna P. Lyubina Anastasiia S. Sapunova Dinara F. Abramova Vladimir V. Zobov Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity Nanomaterials aminophosphonium salt liposome solid lipid nanoparticle anticancer activity apoptosis antimicrobial activity |
| title | Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity |
| title_full | Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity |
| title_fullStr | Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity |
| title_full_unstemmed | Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity |
| title_short | Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity |
| title_sort | novel mitochondria targeted amphiphilic aminophosphonium salts and lipids nanoparticles synthesis antitumor activity and toxicity |
| topic | aminophosphonium salt liposome solid lipid nanoparticle anticancer activity apoptosis antimicrobial activity |
| url | https://www.mdpi.com/2079-4991/13/21/2840 |
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