<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">oncotomsk</journal-id><journal-title-group><journal-title xml:lang="ru">Сибирский онкологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Siberian journal of oncology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1814-4861</issn><issn pub-type="epub">2312-3168</issn><publisher><publisher-name>Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21294/1814-4861-2021-20-4-73-83</article-id><article-id custom-type="elpub" pub-id-type="custom">oncotomsk-1867</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LABORATORY AND EXPERIMENTAL STUDIES</subject></subj-group></article-categories><title-group><article-title>ЦИТОТОКСИЧЕСКИЕ СВОЙСТВА НАНОЛИСТОВЫХ СТРУКТУР НА ОСНОВЕ ОКСИДНЫХ И ГИДРОКСИДНЫХ ФАЗ АЛЮМИНИЯ В ОТНОШЕНИИ ОПУХОЛЕВЫХ КЛЕТОК</article-title><trans-title-group xml:lang="en"><trans-title>CYTOTOXIC PROPERTIES OF NANOSTRUCTURES BASED ON ALUMINUM OXIDE AND HYDROXIDE PHASES IN RELATION TO TUMOR CELLS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1564-0858</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ложкомоев</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Lozhkomoev</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p> кандидат химических наук, заведующий лабораторией</p><p>Researcher ID (WOS): O-3024-2013. Author ID (Scopus): 26664893000</p><p> Россия, 634055, г. Томск, пр. Академический, 2/4 </p></bio><bio xml:lang="en"><p> PhD</p><p> Researcher ID (WOS): O-3024-2013. Author ID (Scopus): 26664893000 </p><p>2/41, Akademicheskiy Ave., 634055, Tomsk, Russia</p></bio><email xlink:type="simple">asl@ispms.tsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бакина</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Bakina</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> кандидат химических наук, научный сотрудник</p><p> SPIN-код: 9002-1344. Researcher ID (WOS): A-3184-2014. Author ID (Scopus): 57200860509 </p><p> Россия, 634055, г. Томск, пр. Академический, 2/4 </p></bio><bio xml:lang="en"><p> DSc, Researcher</p><p>Researcher ID (WOS): A-3184-2014. Author ID (Scopus): 57200860509 </p><p>2/41, Akademicheskiy Ave., 634055, Tomsk, Russia</p></bio><email xlink:type="simple">ovbakina@ispms.tsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1728-7947</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Казанцев</surname><given-names>С. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Kazantsev</surname><given-names>S. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p> младший научный сотрудник</p><p>SPIN-код: 25290738. Researcher ID (WOS): A-9259-2019. Author ID (Scopus): 56985661000</p><p> Россия, 634055, г. Томск, пр. Академический, 2/4 </p></bio><bio xml:lang="en"><p> Junior Researcher</p><p>Researcher ID (WOS): A-9259-2019. Author ID (Scopus): 56985661000 </p><p>2/41, Akademicheskiy Ave., 634055, Tomsk, Russia</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1953-307X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванова</surname><given-names>Л. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanova</surname><given-names>L. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p> младший научный сотрудник</p><p> AuthorID (РИНЦ): 745429. Researcher ID (WOS): E-5777-2014. Author ID (Scopus): 55793393700</p><p> Россия, 634055, г. Томск, пр. Академический, 2/4 </p></bio><bio xml:lang="en"><p> Junior Researcher</p><p>Researcher ID (WOS): E-5777-2014. Author ID (Scopus): 55793393700 </p><p>2/41, Akademicheskiy Ave., 634055, Tomsk, Russia</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7301-7581</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Августинович</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Avgustinovich</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> кандидат медицинских наук, старший научный сотрудник</p><p>SPIN-код: 2952-6119. Researcher ID (WOS): D-6062-2012. Author ID (Scopus): 56392965300</p><p> Россия, 634009. г. Томск, пер. Кооперативный, 5 </p></bio><bio xml:lang="en"><p> MD, PhD, Senior Researcher, Department of Abdominal Oncology</p><p>Researcher ID (WOS): D-6062-2012. Author ID (Scopus): 56392965300</p><p>5, Kooperativny Per., 634009, Tomsk, Russia</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4701-0375</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Афанасьев</surname><given-names>С. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Afanasyev</surname><given-names>S. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, профессор, заведующий отделением абдоминальной онкологии</p><p>SPIN-код: 9206-3037. Researcher ID (WOS): D-2084-2012. Author ID (Scopus): 21333316900</p><p> Россия, 634009. г. Томск, пер. Кооперативный, 5 </p></bio><bio xml:lang="en"><p> MD, DSc, Professor, Head of the Department of Abdominal Oncology</p><p>Researcher ID: D-2084-2012. Author ID (Scopus): 21333316900 </p><p>5, Kooperativny Per., 634009, Tomsk, Russia</p></bio><email xlink:type="simple">afanasievsg@oncology.tomsk.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5269-736X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Спирина</surname><given-names>Л. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Spirina</surname><given-names>L. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, ведущий научный сотрудник</p><p>SPINкод: 1336-8363. Researcher ID (WOS): A-7760-2012. Author ID (Scopus): 36960462500</p><p> Россия, 634009. г. Томск, пер. Кооперативный, 5 </p></bio><bio xml:lang="en"><p> DSc, Senior Researcher, Laboratory of Tumor Biochemistry</p><p>Researcher ID (WOS): A-7760-2012. Author ID (Scopus): 36960462500 </p><p>5, Kooperativny Per., 634009, Tomsk, Russia</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2748-0644</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Добродеев</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Dobrodeev</surname><given-names>A. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, ведущий научный сотрудник отделения абдоминальной онкологии</p><p>SPIN-код: 5510-4043. AuthorID (РИНЦ): 312703. Researcher ID (WOS): B-5644-2017. Author ID (Scopus): 24832974200 </p><p> Россия, 634009. г. Томск, пер. Кооперативный, 5 </p></bio><bio xml:lang="en"><p> MD, DSc, Leading Researcher, Department of Abdominal Oncology</p><p>Researcher ID (WOS): B-5644-2017. Author ID (Scopus): 24832974200 </p><p>5, Kooperativny Per., 634009, Tomsk, Russia</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Институт физики прочности и материаловедения Сибирского отделения Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Strength Physics and Materials Science, Siberian Branch of the Russian Academy of Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>27</day><month>08</month><year>2021</year></pub-date><volume>20</volume><issue>4</issue><fpage>73</fpage><lpage>83</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ложкомоев А.С., Бакина О.В., Казанцев С.О., Иванова Л.Ю., Августинович А.В., Афанасьев С.Г., Спирина Л.В., Добродеев А.Ю., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Ложкомоев А.С., Бакина О.В., Казанцев С.О., Иванова Л.Ю., Августинович А.В., Афанасьев С.Г., Спирина Л.В., Добродеев А.Ю.</copyright-holder><copyright-holder xml:lang="en">Lozhkomoev A.S., Bakina O.V., Kazantsev S.O., Ivanova L.Y., Avgustinovich A.V., Afanasyev S.G., Spirina L.V., Dobrodeev A.Y.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.siboncoj.ru/jour/article/view/1867">https://www.siboncoj.ru/jour/article/view/1867</self-uri><abstract><sec><title>Введение</title><p>Введение. Применение наночастиц и наноструктур в качестве компонентов терапии опухолей является предметом большого количества научных исследований. Одним из наиболее перспективных подходов подавления жизнеспособности опухолевых клеток является изменение величины водородного показателя рН их микроокружения при добавлении наночастиц и наноструктур. Гидроксиды и оксиды алюминия имеют ряд преимуществ перед другими частицами благодаря развитой поверхности, низкой токсичности и термической стабильности.</p><p>Целью исследования явилось изучение влияния кислотно-основных свойств нанолистовых структур на основе гидроксидов алюминия с различным фазовым составом на жизнеспособность широкого спектра опухолевых клеток: Hela, mda, pymt, А549, B16F10.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. В качестве прекурсора для получения наноструктур различного фазового состава использовали наночастицы алюмонитридной композиции. Наночастицы алюминия были получены электрическим взрывом алюминиевой проволоки в атмосфере азота. Такие наночастицы реагируют с водой уже при температуре 60 °Ϲ. В результате формируются пористые наноструктуры, которые представляют собой агломераты нанолистов с планарным размером до 200 нм и толщиной 5 нм. Фазовый состав наноструктур варьировали температурой прокаливания. Изменение фазового состава наноструктур приводило к изменению кислотно-основного покрова их поверхности. Для оценки количества кислотных и основных центров на поверхности наноструктур использовали адсорбцию индикаторов Гаммета. Количество адсорбированных красителей определяли спектрофотометрически.</p></sec><sec><title>Результаты</title><p>Результаты. Отличия кислотно-основных характеристик поверхности синтезированных наноструктур приводят к изменению их цитотоксичности в отношении опухолевых клеток. У гидроксида алюминия в фазе γ-al2o3 основных центров было в 6,5 раза больше, чем кислотных, что обусловливает его способность проявлять более выраженные антацидные свойства, т.е. дольше нейтрализовать протоны, выделяемые опухолевыми клетками. Данный образец обладает наибольшей активностью в отношении всех клеточных линий.</p></sec><sec><title>Заключение</title><p>Заключение. Противоопухолевая активность синтезированных наноструктур обусловлена не только повышением величины рН микроокружения клеток, но и возможностью дольше поддерживать щелочность микроокружения за счет адсорбции протонов, выделяемых опухолевыми клетками.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. Currently, the use of nanoparticles and nanostructures as components of tumor therapy is the subject of numerous scientific articles. To change the parameters of cell microenvironment in presence of nanoparticles and nanostructures is a promising approach to reducing the tumor cell viability. Aluminum hydroxides and oxides have a number of advantages over other particles due to their porous surface, low toxicity, and thermal stability.</p><p>The purpose of the study was to investigate the influence of the acid-base properties of aluminum hydroxide structures with different phase composition on the tumor cell viability (Hela, mda, pymt, a549, B16F10).</p></sec><sec><title>Material and methods</title><p>Material and methods. Aln/al nanoparticles were used as a precursor for obtaining structures with various phase compositions. The anoparticles were produced by electric explosion of an aluminum wire in a nitrogen atmosphere. Such nanoparticles interact with water at 60 °Ϲ, resulting in formation of porous nanostructures. They are agglomerates of nanosheets with a planar size of up to 200 nm and a thickness of 5 nm. The phase composition of the structures was varied by the calcination temperature. A change in the phase composition of nanostructures led to a change in the acid-base properties of their surface. To estimate the number of acidic and basic centers on the surface of nanostructures, the adsorption of Hammett indicators was used. The amount of adsorbed dyes was determined spectrophotometrically.</p></sec><sec><title>Results</title><p>Results. It was found that the differences in the acid-base characteristics of the surface of the nanostructures led to a change in their antitumor activity. Γ-al2o3 had 6.5 times more basic centers than acidic ones, which determined its ability to exhibit more pronounced antacid properties, i.e. Longer to neutralize protons secreted by tumor cells. This sample had the highest antitumor activity against all tested cell lines.</p></sec><sec><title>Conclusion</title><p>Conclusion. The antitumor activity of synthesized structures was found to be related not only to an increase in the ph of the cell microenvironment, but also to the ability to maintain the alkalinity of the microenvironment for a longer time due to the adsorption of protons released by tumor cells.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>наноструктуры</kwd><kwd>цитотоксичность</kwd><kwd>кислотно-основные свойства</kwd><kwd>опухолевые клетки</kwd></kwd-group><kwd-group xml:lang="en"><kwd>nanostructures</kwd><kwd>antitumor activity</kwd><kwd>acid and base properties</kwd><kwd>cell microenvironment</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках государственного задания ИФПМ СО РАН, тема номер FWRW-2019- 0033.</funding-statement><funding-statement xml:lang="en">The work was carried out within the framework of the state assignment of the ISPMS SB RAS (FWRW- 2019- 0033).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Davis M.E., Chen Z.G., Shin D.M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008 Sep; 7(9): 771–82. doi: 10.1038/nrd2614.</mixed-citation><mixed-citation xml:lang="en">Davis M.E., Chen Z.G., Shin D.M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008 Sep; 7(9): 771–82. doi: 10.1038/nrd2614.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Cho Y., Lee J.B., Hong J. Controlled release of an anti-cancer drug from DNA structured nano-films. Sci Rep. 2014 Feb 12; 4: 4078. doi: 10.1038/srep04078.</mixed-citation><mixed-citation xml:lang="en">Cho Y., Lee J.B., Hong J. Controlled release of an anti-cancer drug from DNA structured nano-films. Sci Rep. 2014 Feb 12; 4: 4078. doi: 10.1038/srep04078.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Shu Y., Shu D., Haque F., Guo P. Fabrication of pRNA nanoparticles to deliver therapeutic RNAs and bioactive compounds into tumor cells. Nat Protoc. 2013 Sep; 8(9): 1635–59. doi: 10.1038/nprot.2013.097.</mixed-citation><mixed-citation xml:lang="en">Shu Y., Shu D., Haque F., Guo P. Fabrication of pRNA nanoparticles to deliver therapeutic RNAs and bioactive compounds into tumor cells. Nat Protoc. 2013 Sep; 8(9): 1635–59. doi: 10.1038/nprot.2013.097.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Hauert S., Bhatia S.N. Mechanisms of cooperation in cancer nanomedicine: towards systems nanotechnology. Trends Biotechnol. 2014 Sep; 32(9): 448–55. doi: 10.1016/j.tibtech.2014.06.010.</mixed-citation><mixed-citation xml:lang="en">Hauert S., Bhatia S.N. Mechanisms of cooperation in cancer nanomedicine: towards systems nanotechnology. Trends Biotechnol. 2014 Sep; 32(9): 448–55. doi: 10.1016/j.tibtech.2014.06.010.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Mikhaylov G., Klimpel D., Schaschke N., Mikac U., Vizovisek M., Fonovic M., Turk V., Turk B., Vasiljeva O. Selective targeting of tumor and stromal cells by a nanocarrier system displaying lipidated cathepsin B inhibitor. Angew Chem Int Ed Engl. 2014 Sep 15; 53(38): 10077–81. doi: 10.1002/anie.201402305.</mixed-citation><mixed-citation xml:lang="en">Mikhaylov G., Klimpel D., Schaschke N., Mikac U., Vizovisek M., Fonovic M., Turk V., Turk B., Vasiljeva O. Selective targeting of tumor and stromal cells by a nanocarrier system displaying lipidated cathepsin B inhibitor. Angew Chem Int Ed Engl. 2014 Sep 15; 53(38): 10077–81. doi: 10.1002/anie.201402305.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Mikhaylov G., Mikac U., Magaeva A.A., Itin V.I., Naiden E.P., Psakhye I., Babes L., Reinheckel T., Peters C., Zeiser R., Bogyo M., Turk V., Psakhye S.G., Turk B., Vasiljeva O. Ferri-liposomes as an MRI-visible drugdelivery system for targeting tumours and their microenvironment. Nat Nanotechnol. 2011 Aug 7; 6(9): 594–602. doi: 10.1038/nnano.2011.112.</mixed-citation><mixed-citation xml:lang="en">Mikhaylov G., Mikac U., Magaeva A.A., Itin V.I., Naiden E.P., Psakhye I., Babes L., Reinheckel T., Peters C., Zeiser R., Bogyo M., Turk V., Psakhye S.G., Turk B., Vasiljeva O. Ferri-liposomes as an MRI-visible drugdelivery system for targeting tumours and their microenvironment. Nat Nanotechnol. 2011 Aug 7; 6(9): 594–602. doi: 10.1038/nnano.2011.112.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Kumar C.S., Mohammad F. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Adv Drug Deliv Rev. 2011 Aug 14; 63(9): 789–808. doi: 10.1016/j.addr.2011.03.008.</mixed-citation><mixed-citation xml:lang="en">Kumar C.S., Mohammad F. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Adv Drug Deliv Rev. 2011 Aug 14; 63(9): 789–808. doi: 10.1016/j.addr.2011.03.008.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Verma A., Stellacci F. Effect of surface properties on nanoparticle-cell interactions. Small. 2010 Jan; 6(1): 12–21. doi: 10.1002/smll.200901158.</mixed-citation><mixed-citation xml:lang="en">Verma A., Stellacci F. Effect of surface properties on nanoparticle-cell interactions. Small. 2010 Jan; 6(1): 12–21. doi: 10.1002/smll.200901158.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Patra H.K., Dasgupta A.K. Cancer cell response to nanoparticles: criticality and optimality. Nanomedicine. 2012 Aug; 8(6): 842–52. doi: 10.1016/j.nano.2011.10.009.</mixed-citation><mixed-citation xml:lang="en">Patra H.K., Dasgupta A.K. Cancer cell response to nanoparticles: criticality and optimality. Nanomedicine. 2012 Aug; 8(6): 842–52. doi: 10.1016/j.nano.2011.10.009.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Petros R.A., DeSimone J.M. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010 Aug; 9(8): 615–27. doi: 10.1038/nrd2591.</mixed-citation><mixed-citation xml:lang="en">Petros R.A., DeSimone J.M. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010 Aug; 9(8): 615–27. doi: 10.1038/nrd2591.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Li Y., Tian Y., Nie G. Antineoplastic activities of Gd@C(OH) nanoparticles: tumor microenvironment regulation. Sci China Life Sci. 2012 Oct; 55(10): 884–90. doi: 10.1007/s11427-012-4387-7.</mixed-citation><mixed-citation xml:lang="en">Li Y., Tian Y., Nie G. Antineoplastic activities of Gd@C(OH) nanoparticles: tumor microenvironment regulation. Sci China Life Sci. 2012 Oct; 55(10): 884–90. doi: 10.1007/s11427-012-4387-7.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Li M., Ren L., Li L., He P., Lan G., Zhang Y., Yang K. Cytotoxic Effect on Osteosarcoma MG-63 Cells by Degradation of Magnesium. J Materials Scien Technol. 2014; 30(9): 888–93. doi: 10.1016/j.jmst.2014.04.010.</mixed-citation><mixed-citation xml:lang="en">Li M., Ren L., Li L., He P., Lan G., Zhang Y., Yang K. Cytotoxic Effect on Osteosarcoma MG-63 Cells by Degradation of Magnesium. J Materials Scien Technol. 2014; 30(9): 888–93. doi: 10.1016/j.jmst.2014.04.010.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Y., Ren L., Li M., Lin X., Zhao H., Yang K. Preliminary study on cytotoxic effect of biodegradation of magnesium on cancer cells. J Materials Scien Technol. 2012; 28(9): 769–72. doi: 10.1016/S1005-0302(12)60128-5.</mixed-citation><mixed-citation xml:lang="en">Zhang Y., Ren L., Li M., Lin X., Zhao H., Yang K. Preliminary study on cytotoxic effect of biodegradation of magnesium on cancer cells. J Materials Scien Technol. 2012; 28(9): 769–72. doi: 10.1016/S1005-0302(12)60128-5.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Sonveaux P., Végran F., Schroeder T., Wergin M.C., Verrax J., Rabbani Z.N., De Saedeleer C.J., Kennedy K.M., Diepart C., Jordan B.F., Kelley M.J., Gallez B., Wahl M.L., Feron O., Dewhirst M.W. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 2008 Dec; 118(12): 3930–42. doi: 10.1172/JCI36843.</mixed-citation><mixed-citation xml:lang="en">Sonveaux P., Végran F., Schroeder T., Wergin M.C., Verrax J., Rabbani Z.N., De Saedeleer C.J., Kennedy K.M., Diepart C., Jordan B.F., Kelley M.J., Gallez B., Wahl M.L., Feron O., Dewhirst M.W. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 2008 Dec; 118(12): 3930–42. doi: 10.1172/JCI36843.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Gillies R.J., Raghunand N., Garcia-Martin M.L., Gatenby R.A. pH imaging. A review of pH measurement methods and applications in cancers. IEEE Eng Med Biol Mag. 2004; 23(5): 57–64. doi: 10.1109/memb.2004.1360409.</mixed-citation><mixed-citation xml:lang="en">Gillies R.J., Raghunand N., Garcia-Martin M.L., Gatenby R.A. pH imaging. A review of pH measurement methods and applications in cancers. IEEE Eng Med Biol Mag. 2004; 23(5): 57–64. doi: 10.1109/memb.2004.1360409.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">De Milito A., Canese R., Marino M.L., Borghi M., Iero M., Villa A., Venturi G., Lozupone F., Iessi E., Logozzi M., Della Mina P., Santinami M., Rodolfo M., Podo F., Rivoltini L., Fais S. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer. 2010 Jul 1; 127(1): 207–19. doi: 10.1002/ijc.25009.</mixed-citation><mixed-citation xml:lang="en">De Milito A., Canese R., Marino M.L., Borghi M., Iero M., Villa A., Venturi G., Lozupone F., Iessi E., Logozzi M., Della Mina P., Santinami M., Rodolfo M., Podo F., Rivoltini L., Fais S. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer. 2010 Jul 1; 127(1): 207–19. doi: 10.1002/ijc.25009.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Spugnini E.P., Buglioni S., Carocci F., Francesco M., Vincenzi B., Fanciulli M., Fais S. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med. 2014 Aug 21; 12: 225. doi: 10.1186/s12967-014-0225-y.</mixed-citation><mixed-citation xml:lang="en">Spugnini E.P., Buglioni S., Carocci F., Francesco M., Vincenzi B., Fanciulli M., Fais S. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med. 2014 Aug 21; 12: 225. doi: 10.1186/s12967-014-0225-y.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Meng H., Mai W.X., Zhang H., Xue M., Xia T., Lin S., Wang X., Zhao Y., Ji Z., Zink J.I., Nel A.E. Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano. 2013; 7(2): 994–1005. doi: 10.1021/nn3044066.</mixed-citation><mixed-citation xml:lang="en">Meng H., Mai W.X., Zhang H., Xue M., Xia T., Lin S., Wang X., Zhao Y., Ji Z., Zink J.I., Nel A.E. Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano. 2013; 7(2): 994–1005. doi: 10.1021/nn3044066.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Khawar I.A., Kim J.H., Kuh H.J. Improving drug delivery to solid tumors: priming the tumor microenvironment. J Control Release. 2015 Mar 10; 201: 78–89. doi: 10.1016/j.jconrel.2014.12.018.</mixed-citation><mixed-citation xml:lang="en">Khawar I.A., Kim J.H., Kuh H.J. Improving drug delivery to solid tumors: priming the tumor microenvironment. J Control Release. 2015 Mar 10; 201: 78–89. doi: 10.1016/j.jconrel.2014.12.018.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Kim S.S., Rait A., Kim E., Pirollo K.F., Chang E.H. A tumortargeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme. Nanomedicine. 2015 Feb; 11(2): 301–11. doi: 10.1016/j.nano.2014.09.005.</mixed-citation><mixed-citation xml:lang="en">Kim S.S., Rait A., Kim E., Pirollo K.F., Chang E.H. A tumortargeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme. Nanomedicine. 2015 Feb; 11(2): 301–11. doi: 10.1016/j.nano.2014.09.005.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Kanamala M., Wilson W.R., Yang M., Palmer B.D., Wu Z. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. Biomaterials. 2016 Apr; 85: 152–67. doi: 10.1016/j.biomaterials.2016.01.061.</mixed-citation><mixed-citation xml:lang="en">Kanamala M., Wilson W.R., Yang M., Palmer B.D., Wu Z. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. Biomaterials. 2016 Apr; 85: 152–67. doi: 10.1016/j.biomaterials.2016.01.061.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Taylor S., Spugnini E.P., Assaraf Y.G., Azzarito T., Rauch C., Fais S. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resist Updat. 2015 Nov; 23: 69–78. doi: 10.1016/j.drup.2015.08.004.</mixed-citation><mixed-citation xml:lang="en">Taylor S., Spugnini E.P., Assaraf Y.G., Azzarito T., Rauch C., Fais S. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resist Updat. 2015 Nov; 23: 69–78. doi: 10.1016/j.drup.2015.08.004.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Walsh M., Fais S., Spugnini E.P., Harguindey S., Abu Izneid T., Scacco L., Williams P., Allegrucci C., Rauch C., Omran Z. Proton pump inhibitors for the treatment of cancer in companion animals. J Exp Clin Cancer Res. 2015 Sep 4; 34(1): 93. doi: 10.1186/s13046-015-0204-z.</mixed-citation><mixed-citation xml:lang="en">Walsh M., Fais S., Spugnini E.P., Harguindey S., Abu Izneid T., Scacco L., Williams P., Allegrucci C., Rauch C., Omran Z. Proton pump inhibitors for the treatment of cancer in companion animals. J Exp Clin Cancer Res. 2015 Sep 4; 34(1): 93. doi: 10.1186/s13046-015-0204-z.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Bakina O.V., Svarovskaya N.V., Glazkova E.A., Lozhkomoev A.S. Flower-shaped ALOOH nanostructures synthesized by the reaction of an AlN/Al composite nanopowder in water. Advanced Powder Technology. 2015; 26(6): 1512–19. doi: 10.1186/s13046-015-0204-z.</mixed-citation><mixed-citation xml:lang="en">Bakina O.V., Svarovskaya N.V., Glazkova E.A., Lozhkomoev A.S. Flower-shaped ALOOH nanostructures synthesized by the reaction of an AlN/Al composite nanopowder in water. Advanced Powder Technology. 2015; 26(6): 1512–19. doi: 10.1186/s13046-015-0204-z.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Lerner M.I., Pervikov A.V., Lozhkomoev A.S., Bakina O.V. Synthesis of Al nanoparticles and Al/AlN composite nanoparticles by electrical explosion of aluminum wires in argon and nitrogen. Advanced Powder Technology. 2016; 295: 307–314. doi: 10.1016/j.powtec.2016.04.005.</mixed-citation><mixed-citation xml:lang="en">Lerner M.I., Pervikov A.V., Lozhkomoev A.S., Bakina O.V. Synthesis of Al nanoparticles and Al/AlN composite nanoparticles by electrical explosion of aluminum wires in argon and nitrogen. Advanced Powder Technology. 2016; 295: 307–314. doi: 10.1016/j.powtec.2016.04.005.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Tsybulya S.V., Kryukova G.N. Nanocrystalline transition aluminas: Nanostructure and features of x-ray powder diffraction patterns of low-temperature Al2O3 polymorphs. Physical Review B. 2008; 77(2); 024112–024125. doi: 10.1103/PhysRevB.77.024112.</mixed-citation><mixed-citation xml:lang="en">Tsybulya S.V., Kryukova G.N. Nanocrystalline transition aluminas: Nanostructure and features of x-ray powder diffraction patterns of low-temperature Al2O3 polymorphs. Physical Review B. 2008; 77(2); 024112–024125. doi: 10.1103/PhysRevB.77.024112.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang S., Li J., Lykotrafitis G., Bao G., Suresh S. Size-Dependent Endocytosis of Nanoparticles. Adv Mater. 2009; 21: 419–424. doi: 10.1002/adma.200801393.</mixed-citation><mixed-citation xml:lang="en">Zhang S., Li J., Lykotrafitis G., Bao G., Suresh S. Size-Dependent Endocytosis of Nanoparticles. Adv Mater. 2009; 21: 419–424. doi: 10.1002/adma.200801393.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Jiang W., Kim B.Y., Rutka J.T., Chan W.C. Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol. 2008 Mar; 3(3): 145–50. doi: 10.1038/nnano.2008.30.</mixed-citation><mixed-citation xml:lang="en">Jiang W., Kim B.Y., Rutka J.T., Chan W.C. Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol. 2008 Mar; 3(3): 145–50. doi: 10.1038/nnano.2008.30.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
