KFU. Card publication. Novel mitochondria-targeted amphiphilic aminophosphonium salts and lipids nanoparticles: synthesis, antitumor activity and toxicity

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NOVEL MITOCHONDRIA-TARGETED AMPHIPHILIC AMINOPHOSPHONIUM SALTS AND LIPIDS NANOPARTICLES: SYNTHESIS, ANTITUMOR ACTIVITY AND TOXICITY

Form of presentation

Articles in international journals and collections

Year of publication

2023

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Authors, employees of KFU

Mironov Vladimir Fedorovich, author

Bibliographic description in the original language

V.F.Mironov, M.N.Dimukhametov, A.V.Nemtarev, T.N.Pashirova, O.V.Tsepaeva, A.D. Voloshina, A.B.Vyshtakalyuk, I.A.Litvinov, A.P.Lyubina, A.S.Sapunova, D.F.Abramova, V.V.Zobov. Novel mitochondria-targeted amphiphilic aminophosphonium salts and lipids nanoparticles: synthesis, antitumor activity and toxicity. // Nanomaterials. 2023, 13, 2840. Doi 10.3390/nano13212840.

Annotation

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 IC50s 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 S. aureus 209P and B. segeus 8035, including methicillin-resistant S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead APP.

Keywords

aminophosphonium salt; liposome, solid lipid nanoparticle, anticancer activity, apoptosis, antimicrobial activity, hemolytic activity, acute toxicity

The name of the journal

Nanomaterials

URL

https://doi.org/10.3390/nano13212840

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=306758&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Mironov Vladimir Fedorovich	ru_RU
dc.date.accessioned	2023-01-01T00:00:00Z	ru_RU
dc.date.available	2023-01-01T00:00:00Z	ru_RU
dc.date.issued	2023	ru_RU
dc.identifier.citation	V.F.Mironov, M.N.Dimukhametov, A.V.Nemtarev, T.N.Pashirova, O.V.Tsepaeva, A.D. Voloshina, A.B.Vyshtakalyuk, I.A.Litvinov, A.P.Lyubina, A.S.Sapunova, D.F.Abramova, V.V.Zobov. Novel mitochondria-targeted amphiphilic aminophosphonium salts and lipids nanoparticles: synthesis, antitumor activity and toxicity. // Nanomaterials. 2023, 13, 2840. Doi 10.3390/nano13212840.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=306758&p_lang=2	ru_RU
dc.description.abstract	Nanomaterials	ru_RU
dc.description.abstract	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 IC50s 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 S. aureus 209P and B. segeus 8035, including methicillin-resistant S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead APP.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	aminophosphonium salt; liposome	ru_RU
dc.subject	solid lipid nanoparticle	ru_RU
dc.subject	anticancer activity	ru_RU
dc.subject	apoptosis	ru_RU
dc.subject	antimicrobial activity	ru_RU
dc.subject	hemolytic activity	ru_RU
dc.subject	acute toxicity	ru_RU
dc.title	Novel mitochondria-targeted amphiphilic aminophosphonium salts and lipids nanoparticles: synthesis, antitumor activity and toxicity	ru_RU
dc.type	Articles in international journals and collections	ru_RU