Mitochondria-targeted mesoporous silica nanoparticles noncovalently modified with triphenylphosphonium cation: Physicochemical characteristics, cytotoxicity and intracellular uptake
| Autor: | Konstantin A. Petrov, Leysan A. Vasileva, Anastasiia S. Sapunova, Alexander A. Lamberov, Ayrat R. Khamatgalimov, M. P. Danilaev, Alina F. Saifina, S. R. Egorova, Lucia Ya. Zakharova, Gusel V. Sibgatullina, A. R. Ibragimova, Oleg G. Sinyashin, Alexandra D. Voloshina, Anna A. Tyryshkina, Aidar T. Gubaidullin, Dinar R. Gabdrakhmanov, Dmitry V. Samigullin, F. G. Valeeva |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmaceutical Science
Nanoparticle 02 engineering and technology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Cations Rhodamine B Humans Phosphonium Cytotoxicity Drug Carriers Mesoporous silica 021001 nanoscience & nanotechnology Silicon Dioxide Mitochondria chemistry Cancer cell Surface modification Nanoparticles Female 0210 nano-technology Mesoporous material Porosity Nuclear chemistry HeLa Cells |
| Zdroj: | International journal of pharmaceutics. 604 |
| ISSN: | 1873-3476 |
| Popis: | Novel nanocomposite system based on mesoporous silica nanoparticles (MSNs) noncovalently modified with hexadecyltriphenylphosphonium bromide (HTPPB) has been prepared, thoroughly characterized and used for encapsulation of model cargo Rhodamine B (RhB). The high encapsulation efficacy of this dye by HTPPB-modified mesoporous particles was demonstrated by spectrophotometry and thermography techniques. The bioavailability of MSN@HTPPB was testified. Cytotoxicity assay revealed that a marked suppression of M−HeLa cancer cells (epithelioid carcinoma of the cervix) occurs at concentration of 0.06 μg/mL, while the higher viability of Chang liver normal cell line was preserved in the concentration range of 0.98–0.06 μg/mL. Hemolysis assay demonstrated that only 2% of red blood cells are destructed at ~ 30 μg/mL concentration. This allows us to select the most harmless compositions based on MSN@HTPPB with minimal side effects toward normal cells and recommend them for the development of antitumor formulations. Fluorescence microscopy technique testified satisfactory penetration of HTPPB-modified carriers into M−HeLa cells. Importantly, modification of the MSN with HTPPB is shown to promote efficient delivery to mitochondria. To the best of our knowledge, it is one of the first successful examples of noncovalent surface modification of the MSNs with lipophilic phosphonium cation that improves targeted delivery of loads to mitochondria. |
| Databáze: | OpenAIRE |
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