chemicallytechFine Chemical TechnologiesТонкие химические технологии2410-65932686-7575MIREA – Russian Technological University (RTU MIREA).10.32362/2410-6593-2020-15-1-7-27chemicallytech-1582Research ArticleREVIEW ARTICLESОБЗОРНЫЕ СТАТЬИСationic liposomes as delivery systems for nucleic acidsКатионные липосомы как средства доставки нуклеиновых кислотhttps://orcid.org/0000-0001-9466-0824МихеевА. А.MikheevA. A.

Михеев Алексей Александрович, научный сотрудник 4-го научно-исследовательского отдела.

107014, Москва, ул. Большая Оленья, д. 8

Aleksey A. Mikheev, Researcher, The 4th Research Department.

8, Bolshaya Olenya ul., Moscow, 107014

aa-mixeev@mail.ruhttps://orcid.org/0000-0003-3727-4905ШмендельЕ. В.ShmendelE. V.

Шмендель Елена Васильевна, кандидат химических наук, доцент кафедры химии и технологии биологически активных соединений, медицинской и органической химии им. Н.А. Преображенского Института тонких химических технологий им. М.В. Ломоносова.

119571, Москва, пр-т Вернадского, д. 86

Elena V. Shmendel, Cand. of Sci. (Chemistry), Associate Professor, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies.

86, Vernadskogo pr., Moscow, 119571

elena_shmendel@mail.ruhttps://orcid.org/0000-0002-1297-8562ЖестовскаяЕ. С.ZhestovskayaE. S.

Жестовская Елизавета Сергеевна, научный сотрудник 1-го научно-аналитического отдела.

107014, Москва, ул. Большая Оленья, д. 8

Elizaveta S. Zhestovskaya, Researcher, The 1th Research and Analytical Department.

8, Bolshaya Olenya ul., Moscow, 107014

zhestovskayae@gmail.comhttps://orcid.org/0000-0001-8805-6460НазаровГ. В.NazarovG. V.

Назаров Георгий Валерьевич, доктор химических наук, главный научный сотрудник.

107014, Москва, ул. Большая Оленья, д. 8

Georgy V. Nazarov, Dr. of Sci. (Chemistry), Chief Researcher.

8, Bolshaya Olenya ul., Moscow, 107014

denis-1000@list.ruhttps://orcid.org/0000-0002-5372-1325МасловМ. А.MaslovM. A.

Маслов Михаил Александрович, доктор химических наук, директор Института тонких химических технологий, профессор кафедры химии и технологии биологически активных соединений, медицинской и органической химии им. Н.А. Преображенского Института тонких химических технологий им. М.В. Ломоносова. Scopus Author ID 7003427092

119571, Москва, пр-т Вернадского, д. 86

Mikhail A. Maslov, Dr. of Sci. (Chemistry), Director of the Institute of Fine Chemical Technologies, Professor at the N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies. Scopus Author ID 7003427092

86, Vernadskogo pr., Moscow, 119571

mamaslov@mail.ruНаучный центр «Сигнал»РоссияScientific Center “Signal”Russian FederationМИРЭА – Российский технологический университет (Институт тонких химических технологий имени М.В. Ломоносова)РоссияMIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)Russian Federation202021032020151727Copyright © Mikheev A.A., Shmendel E.V., Zhestovskaya E.S., Nazarov G.V., Maslov M.A., 20202020Михеев А.А., Шмендель Е.В., Жестовская Е.С., Назаров Г.В., Маслов М.А.Mikheev A.A., Shmendel E.V., Zhestovskaya E.S., Nazarov G.V., Maslov M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.finechem-mirea.ru/jour/article/view/1582Objectives

Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.

Results

Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.

Conclusions

Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.

Цели

Цели. Генная терапия основана на введении генетического материала в клетки, ткани или органы с целью лечения наследственных или приобретенных заболеваний. Ключевым фактором успеха генной терапии является развитие систем доставки, способных эффективно переносить генетический материал к месту их терапевтического действия, не вызывая каких-либо связанных с ними побочных эффектов. За последнее десять лет много усилий было направлено на создание более эффективных и биосовместимых векторов, способных переносить нуклеиновые кислоты в клетки, не вызывая иммунного ответа. Катионные липосомы являются одним из самых универсальных инструментов для доставки нуклеиновых кислот в клетки, однако применение липосом для целей генной терапии ограничено неспецифичностью такой доставки. Это связано с наличием различных биологических барьеров на пути комплекса липосом с нуклеиновыми кислотами; например, с нестабильностью в биологических жидкостях; взаимодействиями с белками сыворотки крови, плазматической и ядерной мембранами; а также с эндосомной деградацией. В этом обзоре обобщены результаты исследований за последние годы по разработкам катионных липосом, эффективных in vitro и in vivo. Особое внимание уделено отдельным структурным элементам катионных липосом, определяющим эффективность трансфекции и цитотоксичность. Целью данного обзора являлось теоретическое обоснование выбора катионных липосом, наиболее перспективных для доставки нуклеиновых кислот в эукариотические клетки, а также изучение влияния состава катионных липидов на эффективность трансфекции in vitro.

Результаты

Результаты. В результате проведенного анализа литературы можно утверждать, что одними из наиболее перспективных систем доставки нуклеиновых кислот являются катионные липиды на основе холестерина и спермина с добавлением липида-хелпера DOPE. Кроме того, было установлено, что варьирование состава катионных липосом, соотношения катионных липидов и нуклеиновых кислот, а также размера и дзета-потенциала липосом оказывают значительное влияние на эффективность трансфекции.

Выводы

Выводы. Дальнейшие исследования в данном направлении должны включать в себя оптимизацию условий получения катионных липосом с учетом установленных закономерностей, а также физико-химических свойств. Необходимо исследовать возможности повышения эффективности доставки нуклеиновых кислот путем поиска оптимальных структур катионных липосом, определения соотношения компонентов липоплексов и изучения свойств и эффективности доставки многокомпонентных липосом in vitro.

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The authors declare that there are no conflicts of interest present.