transmedТрансляционная медицинаTranslational Medicine2311-44952410-5155Almazov National Medical Research Centre, Saint Petersburg, Russia10.18705/2311-4495-2023-10-6-507-521JTTUSStransmed-829Research ArticleМЕДИЦИНСКАЯ ХИМИЯMEDICINAL CHEMISTRYПерспективы применения водорастворимых производных легких фуллеренов в медицине.Prospects for the application of water-soluble derivatives of light fullerenes in medicine.КукалияО. Н.KukaliaO. N.

Кукалия Олег Нугзарович, врач

Oleg N. Kukalia, MD

МещеряковА. А.MeshcheryakovA. A.

Мещеряков Анатолий Анатольевич, к.х.н., младший научный сотрудник

Anatoly A. Meshcheryakov, Ph.D., laboratory assistant

ЮрьевГ. О.IurevG. O.

Юрьев Глеб Олегович, к.х.н., ассистент

Санкт-Петербург, 197022

Gleb O. Iurev, Ph.D., assistant

glebbi407@mail.ruАндоскинП. А.AndoskinP. A.

Андоскин Павел Александрович, к.б.н., ассистент

Pavel A. Andoskin, Ph.D., assistant

СеменовК. Н.SemenovK. N.

Семенов Константин Николаевич, д.х.н., профессор

Konstantin N. Semenov, D.Sc., prof.

МолчановО. Е.MolchanovO. E.

Молчанов Олег Евгеньевич, д.м.н.

Oleg E. Molchanov, MD, PhD

МайстренкоД. Н.MaistrenkoD. N.

Майстренко Дмитрий Николаевич, д.м.н.

Dmitry N. Maistrenko, MD, PhD

МуринИ. В.MurinI. V.

Мурин Игорь Васильевич, д.х.н., профессор

Igor V. Murin, D.Sc., prof., Institute of Chemistry

ШаройкоВ. В.SharoykoV. V.

Шаройко Владимир Владимирович, д.б.н., профессор

Vladimir V. Sharoyko, D.Sc., prof., Academician I. P. Pavlov First Saint Petersburg State Medical University

Федеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияAcademician I. P. Pavlov First Saint Petersburg State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение «Российский научный центр радиологии и хирургических технологий имени академика А. М. Гранова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской ФедерацииРоссияAcademician I. P. Pavlov First Saint Petersburg State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение «Российский научный центр радиологии и хирургических технологий имени академика А. М. Гранова» Министерства здравоохранения Российской ФедерацииРоссияAcademician I. P. Pavlov First Saint Petersburg State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение «Российский научный центр радиологии и хирургических технологий имени академика А. М. Гранова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный университет»РоссияAcademician I. P. Pavlov First Saint Petersburg State Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Российский научный центр радиологии и хирургических технологий имени академика А. М. Гранова» Министерства здравоохранения Российской ФедерацииРоссияRussian Scientific Center for Radiology and Surgical Technologies named after A. M. GranovRussian FederationSaint Petersburg State UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение «Российский научный центр радиологии и хирургических технологий имени академика А. М. Гранова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный университет»РоссияAcademician I. P. Pavlov First Saint Petersburg State Medical University; Russian Scientific Center for Radiology and Surgical Technologies named after A. M. Granov; Saint Petersburg State UniversityRussian Federation202312012024106507521Copyright © Кукалия О.Н., Мещеряков А.А., Юрьев Г.О., Андоскин П.А., Семенов К.Н., Молчанов О.Е., Майстренко Д.Н., Мурин И.В., Шаройко В.В., 20242024Кукалия О.Н., Мещеряков А.А., Юрьев Г.О., Андоскин П.А., Семенов К.Н., Молчанов О.Е., Майстренко Д.Н., Мурин И.В., Шаройко В.В.Kukalia O.N., Meshcheryakov A.A., Iurev G.O., Andoskin P.A., Semenov K.N., Molchanov O.E., Maistrenko D.N., Murin I.V., Sharoyko V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://transmed.almazovcentre.ru/jour/article/view/829

Одними из наиболее перспективных направлений использования фуллеренов и их производных являются биология и медицина. Это связано с тем, что фуллерены обладают высокой реакционной способностью благодаря наличию двойных связей, способных присоединять различные радикалы, и демонстрируют высокую антиоксидантную активность, способность проникать через липидный бислой, модулировать трансмембранный транспорт ионов. В обзоре рассмотрены основные биологические свойства водорастворимых производных легких фуллеренов, определяющие их применение в биомедицине.

One of the most promising areas for the use of fullerenes and their derivatives is biology and medicine. This is due to the fact that fullerenes are highly reactive due to the presence of double bonds capable of attaching various radicals, and demonstrate high antioxidant activity, the ability to penetrate through the lipid bilayer, and modulate transmembrane ion transport. The review considers the main biological properties of water-soluble derivatives of light fullerenes, which determine their application in biomedicine.

аддукты фуллерена с аминокислотамибиосовместимостькарбоксилированный фуллеренфуллеренфуллеренолbiocompatibilitycarboxylated fullerenefullerenefullerene adducts with amino acidsfullerenolРабота выполнена при финансовой поддержке Министерства здравоохранения Российской Федерации (государственное задание по теме «Разработка радиопротектора на основе водорастворимых форм наноуглерода, модифицированных L-аминокислотами. ЕГИСУ: 123020800170-8»).The work was carried out with the financial support of the Ministry of Health of the Russian Federation (state assignment on the topic “Development of a radioprotector based on water-soluble forms of nanocarbon modified with L-amino acids. EGISU: 123020800170-8”).ReferencesPodolsky NE, Marcos MA, Cabaleiro D, et al. Physico-chemical properties of C60(OH)22–24 water solutions: Density, viscosity, refraction index, isobaric heat capacity and antioxidant activity. J Mol Liq. 2019 Mar; 278:342–55. DOI: 10.1016/j.molliq.2018.12.148.Podolsky NE, Marcos MA, Cabaleiro D, et al. Physico-chemical properties of C60(OH)22–24 water solutions: Density, viscosity, refraction index, isobaric heat capacity and antioxidant activity. J Mol Liq. 2019 Mar; 278:342–55. DOI: 10.1016/j.molliq.2018.12.148.Serebryakov EB, Zakusilo DN, Semenov KN, et al. Physico-chemical properties of C70-l-threonine bisadduct (C70(C4H9NO2)2) aqueous solutions. J Mol Liq. 2019 Apr; 279:687–99. DOI: 10.1016/j.molliq.2019.02.013.Serebryakov EB, Zakusilo DN, Semenov KN, et al. Physico-chemical properties of C70-l-threonine bisadduct (C70(C4H9NO2)2) aqueous solutions. J Mol Liq. 2019 Apr; 279:687–99. DOI: 10.1016/j.molliq.2019.02.013.Nikolaev DN, Podolsky NE, Lelet MI, et al. Thermodynamic and quantum chemical investigation of the monocarboxylated fullerene C60CHCOOH. J Chem Thermodyn. 2020 Jan; 140:105898. DOI: 10.1016/j.jct.2019.105898.Nikolaev DN, Podolsky NE, Lelet MI, et al. Thermodynamic and quantum chemical investigation of the monocarboxylated fullerene C60CHCOOH. J Chem Thermodyn. 2020 Jan; 140:105898. DOI: 10.1016/j.jct.2019.105898.Podolsky NE, Lelet MI, Ageev SV, et al. Thermodynamic properties of the C70(OH)12 fullerenol in the temperature range T = 9.2 K to 304.5 K. J Chem Thermodyn. 2020 May; 144:106029. DOI: 10.1016/j.jct.2019.106029.Podolsky NE, Lelet MI, Ageev SV, et al. Thermodynamic properties of the C70(OH)12 fullerenol in the temperature range T = 9.2 K to 304.5 K. J Chem Thermodyn. 2020 May; 144:106029. DOI: 10.1016/j.jct.2019.106029.Podolsky NE, Lelet MI, Ageev SV, et al. Thermodynamic Properties from Calorimetry and Density Functional Theory and the Thermogravimetric Analysis of the Fullerene Derivative C 60 (OH) 40. J Chem Eng Data. 2019 Apr 11;64(4):1480–7. DOI: 10.1021/acs.jced.8b01075.Podolsky NE, Lelet MI, Ageev SV, et al. Thermodynamic Properties from Calorimetry and Density Functional Theory and the Thermogravimetric Analysis of the Fullerene Derivative C 60 (OH) 40. J Chem Eng Data. 2019 Apr 11;64(4):1480–7. DOI: 10.1021/acs.jced.8b01075.Markin AV, Samosudova YS, Ogurtsov TG, et al. Heat capacity and standard thermodynamic functions of the fullerenol C60(OH)24. J Chem Thermodyn. 2020 Oct;149:106192. DOI: 10.1016/j.jct.2020.106192.Markin AV, Samosudova YS, Ogurtsov TG, et al. Heat capacity and standard thermodynamic functions of the fullerenol C60(OH)24. J Chem Thermodyn. 2020 Oct;149:106192. DOI: 10.1016/j.jct.2020.106192.Semenov KN, Charykov NA, Postnov VN, et al. Fullerenols: Physicochemical properties and applications. Prog Solid State Chem. 2016 Jun;44(2):59–74. DOI: 10.1016/j.progsolidstchem.2016.04.002.Semenov KN, Charykov NA, Postnov VN, et al. Fullerenols: Physicochemical properties and applications. Prog Solid State Chem. 2016 Jun;44(2):59–74. DOI: 10.1016/j.progsolidstchem.2016.04.002.Semenov KN, Andrusenko EV, Charykov NA, et al. Carboxylated fullerenes: Physico-chemical properties and potential applications. Prog Solid State Chem. 2017 Dec;47– 48:19–36. DOI: 10.1016/j.progsolidstchem.2017.09.001.Semenov KN, Andrusenko EV, Charykov NA, et al. Carboxylated fullerenes: Physico-chemical properties and potential applications. Prog Solid State Chem. 2017 Dec;47– 48:19–36. DOI: 10.1016/j.progsolidstchem.2017.09.001.Pochkaeva EI, Podolsky NE, Zakusilo DN, et al. Fullerene derivatives with amino acids, peptides and proteins: From synthesis to biomedical application. Prog Solid State Chem. 2020 Mar;57:100255. DOI: 10.1016/j.progsolidstchem.2019.100255.Pochkaeva EI, Podolsky NE, Zakusilo DN, et al. Fullerene derivatives with amino acids, peptides and proteins: From synthesis to biomedical application. Prog Solid State Chem. 2020 Mar;57:100255. DOI: 10.1016/j.progsolidstchem.2019.100255.Sharoyko VV, Ageev SV, Podolsky NE, et al. Biologically active water-soluble fullerene adducts: Das Glasperlenspiel (by H. Hesse) J Mol Liq. 2021 Feb;323:114990. DOI: 10.1016/j.molliq.2020.114990.Sharoyko VV, Ageev SV, Podolsky NE, et al. Biologically active water-soluble fullerene adducts: Das Glasperlenspiel (by H. Hesse) J Mol Liq. 2021 Feb;323:114990. DOI: 10.1016/j.molliq.2020.114990.Bezmel’nitsyn VN, Eletskii AV, Okun’ MV. Fullerenes in solutions. Physics-Uspekhi. 1998 Nov 30;41(11):1091– 114. DOI: 10.1070/PU1998v041n11ABEH000502.Bezmel’nitsyn VN, Eletskii AV, Okun’ MV. Fullerenes in solutions. Physics-Uspekhi. 1998 Nov 30;41(11):1091– 114. DOI: 10.1070/PU1998v041n11ABEH000502.Bagchi D. Bio-nanotechnology: a revolution in food, biomedical, and health sciences. Wiley-Blackwell, 2013. 803 p.Bagchi D. Bio-nanotechnology: a revolution in food, biomedical, and health sciences. Wiley-Blackwell, 2013. 803 p.Semenov KN, Charykov NA, Postnov VN, et al. Fullerenols: Physicochemical properties and applications. Prog Solid State Chem. 2016 Jun;44(2):59–74. DOI: 10.1016/j.progsolidstchem.2016.04.002.Semenov KN, Charykov NA, Postnov VN, et al. Fullerenols: Physicochemical properties and applications. Prog Solid State Chem. 2016 Jun;44(2):59–74. DOI: 10.1016/j.progsolidstchem.2016.04.002.Pochkaeva EI, Podolsky NE, Zakusilo DN, et al. Fullerene derivatives with amino acids, peptides and proteins: From synthesis to biomedical application. Prog Solid State Chem. 2020 Mar;57:100255. DOI: 10.1016/j.progsolidstchem.2019.100255.Pochkaeva EI, Podolsky NE, Zakusilo DN, et al. Fullerene derivatives with amino acids, peptides and proteins: From synthesis to biomedical application. Prog Solid State Chem. 2020 Mar;57:100255. DOI: 10.1016/j.progsolidstchem.2019.100255.Matsubayashi K, Kokubo K, Tategaki H, et al. One-step Synthesis of Water-soluble Fullerenols Bearing Nitrogen-containing Substituents. Fullerenes, Nanotub Carbon Nanostructures. 2009 Jul 1;17(4):440–56. DOI: 10.1080/01490450903039263.Matsubayashi K, Kokubo K, Tategaki H, et al. One-step Synthesis of Water-soluble Fullerenols Bearing Nitrogen-containing Substituents. Fullerenes, Nanotub Carbon Nanostructures. 2009 Jul 1;17(4):440–56. DOI: 10.1080/01490450903039263.Yang XL, Fan CH, Zhu HS. Photo-induced cytotoxicity of malonic acid [C60] fullerene derivatives and its mechanism. Toxicol Vitr. 2002 Feb;16(1):41–6. DOI: 10.1016/S0887-2333(01)00102-3.Yang XL, Fan CH, Zhu HS. Photo-induced cytotoxicity of malonic acid [C60] fullerene derivatives and its mechanism. Toxicol Vitr. 2002 Feb;16(1):41–6. DOI: 10.1016/S0887-2333(01)00102-3.Medzhidova MG, Abdullaeva MV, Fedorova NE, et al. In vitro antiviral activity of fullerene amino acid derivatives in cytomegalovirus infection. Antibiot i khimioterapiia = Antibiot chemoterapy [sic]. 2004;49(8– 9):13–20.Medzhidova MG, Abdullaeva MV, Fedorova NE, et al. In vitro antiviral activity of fullerene amino acid derivatives in cytomegalovirus infection. Antibiot i khimioterapiia = Antibiot chemoterapy [sic]. 2004;49(8– 9):13–20.Lin Y-L, Lei H-Y, Wen Y-Y, et al. Light-Independent Inactivation of Dengue-2 Virus by Carboxyfullerene C3 Isomer. Virology. 2000 Sep;275(2):258–62. DOI: 10.1006/viro.2000.0490.Lin Y-L, Lei H-Y, Wen Y-Y, et al. Light-Independent Inactivation of Dengue-2 Virus by Carboxyfullerene C3 Isomer. Virology. 2000 Sep;275(2):258–62. DOI: 10.1006/viro.2000.0490.Tsao N, Luh T-Y, Chou C-K, et al. Inhibition of Group A Streptococcus Infection by Carboxyfullerene. Antimicrob Agents Chemother. 2001 Jun;45(6):1788–93. DOI: 10.1128/AAC.45.6.1788-1793.2001.Tsao N, Luh T-Y, Chou C-K, et al. Inhibition of Group A Streptococcus Infection by Carboxyfullerene. Antimicrob Agents Chemother. 2001 Jun;45(6):1788–93. DOI: 10.1128/AAC.45.6.1788-1793.2001.Wang IC, Tai LA, Lee DD, et al. C 60 and Water- Soluble Fullerene Derivatives as Antioxidants Against Radical-Initiated Lipid Peroxidation. J Med Chem. 1999 Nov 1;42(22):4614–20. DOI: 10.1021/jm990144s.Wang IC, Tai LA, Lee DD, et al. C 60 and Water- Soluble Fullerene Derivatives as Antioxidants Against Radical-Initiated Lipid Peroxidation. J Med Chem. 1999 Nov 1;42(22):4614–20. DOI: 10.1021/jm990144s.Dugan LL, Turetsky DM, Du C, et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci. 1997 Aug 19;94(17):9434–9. DOI: 10.1073/pnas.94.17.9434.Dugan LL, Turetsky DM, Du C, et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci. 1997 Aug 19;94(17):9434–9. DOI: 10.1073/pnas.94.17.9434.Dugan LL, Lovett EG, Quick KL, et al. Fullerene- based antioxidants and neurodegenerative disorders. Parkinsonism Relat Disord. 2001 Jul;7(3):243–6. DOI: 10.1016/S1353-8020(00)00064-X.Dugan LL, Lovett EG, Quick KL, et al. Fullerene- based antioxidants and neurodegenerative disorders. Parkinsonism Relat Disord. 2001 Jul;7(3):243–6. DOI: 10.1016/S1353-8020(00)00064-X.Käsermann F, Kempf C. Buckminsterfullerene and photodynamic inactivation of viruses. Rev Med Virol. 1998 Jul;8(3):143–51. DOI: 10.1002/(sici)1099-1654(199807/09)8:3<143::aid-rmv214>3.0.co;2-b.Käsermann F, Kempf C. Buckminsterfullerene and photodynamic inactivation of viruses. Rev Med Virol. 1998 Jul;8(3):143–51. DOI: 10.1002/(sici)1099-1654(199807/09)8:3<143::aid-rmv214>3.0.co;2-b.Vileno B, Sienkiewicz A, Lekka M, et al. In vitro assay of singlet oxygen generation in the presence of water-soluble derivatives of C60. Carbon N Y. 2004;42(5– 6):1195–8. DOI: 10.1016/j.carbon.2003.12.042.Vileno B, Sienkiewicz A, Lekka M, et al. In vitro assay of singlet oxygen generation in the presence of water-soluble derivatives of C60. Carbon N Y. 2004;42(5– 6):1195–8. DOI: 10.1016/j.carbon.2003.12.042.Fursov V, Namestnikova D, Kuznetsov DA. In Silico Track to Reveal a Translational Potential of Porphyrin-c60 Nanoparticles in the Ischemic Stroke Related Preclinical Studies. Research Square; 2022. DOI: 10.21203/rs.3.rs-2169685/v1.Fursov V, Namestnikova D, Kuznetsov DA. In Silico Track to Reveal a Translational Potential of Porphyrin-c60 Nanoparticles in the Ischemic Stroke Related Preclinical Studies. Research Square; 2022. DOI: 10.21203/rs.3.rs-2169685/v1.Fursov VV, Zinchenko DI, Namestnikova DD, Kuznetsov DA. „IN SILICO ALGORITHM FOR OPTIMIZATION OF PHARMACOKINETIC STUDIES OF [25Mg2+]PORPHYRIN-FULLERENE NANOPARTICLES“ Bulletin of Russian State Medical University, no. 4, 2022. P. 58–63. DOI: 10.24075/brsmu.2022.037.Fursov VV, Zinchenko DI, Namestnikova DD, Kuznetsov DA. „IN SILICO ALGORITHM FOR OPTIMIZATION OF PHARMACOKINETIC STUDIES OF [25Mg2+]PORPHYRIN-FULLERENE NANOPARTICLES“ Bulletin of Russian State Medical University, no. 4, 2022. P. 58–63. DOI: 10.24075/brsmu.2022.037.Andreev IM, Romanova VS, Petrukhina AO, et al. Amino-acid derivatives of fullerene C60 behave as lipophilic ions penetrating through biomembranes. Phys. Solid State 44, 683–685 (2002). https://doi.org/10.1134/1.1470559Andreev IM, Romanova VS, Petrukhina AO, et al. Amino-acid derivatives of fullerene C60 behave as lipophilic ions penetrating through biomembranes. Phys. Solid State 44, 683–685 (2002). https://doi.org/10.1134/1.1470559Bhakta P, Barthunia B. Fullerene and its applications: A review. Journal of Indian Academy of Oral Medicine and Radiology 32(2):p 15963, Apr–Jun 2020. |DOI: 10.4103/jiaomr.jiaomr_191_19.Bhakta P, Barthunia B. Fullerene and its applications: A review. Journal of Indian Academy of Oral Medicine and Radiology 32(2):p 15963, Apr–Jun 2020. |DOI: 10.4103/jiaomr.jiaomr_191_19.Hou W, Shi G, Wu S, et al. Application of Fullerenes as Photosensitizers for Antimicrobial Photodynamic Inactivation: A Review. Front Microbiol. 2022 Jul 14;13. DOI: 10.3389/fmicb.2022.957698.Hou W, Shi G, Wu S, et al. Application of Fullerenes as Photosensitizers for Antimicrobial Photodynamic Inactivation: A Review. Front Microbiol. 2022 Jul 14;13. DOI: 10.3389/fmicb.2022.957698.Siringan MJ, Dawar A, Zhang J. Interactions between fullerene derivatives and biological systems. Mater Chem Front. 2023;7(11):2153–74. DOI: 10.1039/D3QM00004D.Siringan MJ, Dawar A, Zhang J. Interactions between fullerene derivatives and biological systems. Mater Chem Front. 2023;7(11):2153–74. DOI: 10.1039/D3QM00004D.Giannopoulos GI. Fullerene Derivatives for Drug Delivery against COVID-19: A Molecular Dynamics Investigation of Dendro[60]fullerene as Nanocarrier of Molnupiravir. Nanomaterials. 2022; 12(15):2711. https://doi.org/10.3390/nano12152711Giannopoulos GI. Fullerene Derivatives for Drug Delivery against COVID-19: A Molecular Dynamics Investigation of Dendro[60]fullerene as Nanocarrier of Molnupiravir. Nanomaterials. 2022; 12(15):2711. https://doi.org/10.3390/nano12152711Kazemzadeh H, Mozafari M. Fullerene-based delivery systems. Drug Discov Today. 2019 Mar;24(3):898– 905. DOI: 10.1016/j.drudis.2019.01.013.Kazemzadeh H, Mozafari M. Fullerene-based delivery systems. Drug Discov Today. 2019 Mar;24(3):898– 905. DOI: 10.1016/j.drudis.2019.01.013.Fernandes NB, Shenoy RUK, Kajampady MK, et al. Fullerenes for the treatment of cancer: an emerging tool. Environ Sci Pollut Res 29, 58607–58627 (2022). https://doi.org/10.1007/s11356-022-21449-7Fernandes NB, Shenoy RUK, Kajampady MK, et al. Fullerenes for the treatment of cancer: an emerging tool. Environ Sci Pollut Res 29, 58607–58627 (2022). https://doi.org/10.1007/s11356-022-21449-7Friedman SH, DeCamp DL, Sijbesma RP, et al. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J Am Chem Soc. 1993 Jul 1;115(15):6506–9. DOI: 10.1021/ja00068a005.Friedman SH, DeCamp DL, Sijbesma RP, et al. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J Am Chem Soc. 1993 Jul 1;115(15):6506–9. DOI: 10.1021/ja00068a005.Friedman SH, Ganapathi PS, Rubin Y, Kenyon GL. Optimizing the binding of fullerene inhibitors of the HIV-1 protease through predicted increases in hydrophobic desolvation. J Med Chem. 1998;41(13):2424–2429. DOI: 10.1021/jm970689r.Friedman SH, Ganapathi PS, Rubin Y, Kenyon GL. Optimizing the binding of fullerene inhibitors of the HIV-1 protease through predicted increases in hydrophobic desolvation. J Med Chem. 1998;41(13):2424–2429. DOI: 10.1021/jm970689r.Chien CT, Lee PH, Chen CF, et al. De Novo Demonstration and Co-localization of Free-Radical Production and Apoptosis Formation in Rat Kidney Subjected to Ischemia/Reperfusion. J Am Soc Nephrol. 2001 May;12(5):973–82. DOI: 10.1681/ASN.V125973.Chien CT, Lee PH, Chen CF, et al. De Novo Demonstration and Co-localization of Free-Radical Production and Apoptosis Formation in Rat Kidney Subjected to Ischemia/Reperfusion. J Am Soc Nephrol. 2001 May;12(5):973–82. DOI: 10.1681/ASN.V125973.Chiang LY, Upasani RB, Swirczewski JW. Versatile nitronium chemistry for C60 fullerene functionalization. J Am Chem Soc. 1992 Dec 1;114(26):10154–7. DOI: 10.1021/ja00052a010.Chiang LY, Upasani RB, Swirczewski JW. Versatile nitronium chemistry for C60 fullerene functionalization. J Am Chem Soc. 1992 Dec 1;114(26):10154–7. DOI: 10.1021/ja00052a010.Tsai M-C, Chen YH, Chiang LY. Polyhydroxylated C60, Fullerenol, a Novel Free-radical Trapper, Prevented Hydrogen Peroxide- and Cumene Hydroperoxide-elicited Changes in Rat Hippocampus In-vitro. J Pharm Pharmacol. 2011 Apr 12;49(4):438–45. DOI: 10.1111/j.2042-7158.1997.tb06821.x.Tsai M-C, Chen YH, Chiang LY. Polyhydroxylated C60, Fullerenol, a Novel Free-radical Trapper, Prevented Hydrogen Peroxide- and Cumene Hydroperoxide-elicited Changes in Rat Hippocampus In-vitro. J Pharm Pharmacol. 2011 Apr 12;49(4):438–45. DOI: 10.1111/j.2042-7158.1997.tb06821.x.Mirkov SM, Djordjevic AN, Andric NL, et al. Nitric oxide-scavenging activity of polyhydroxylated fullerenol, C60(OH)24. Nitric Oxide. 2004 Sep;11(2):201–7. DOI: 10.1016/j.niox.2004.08.003.Mirkov SM, Djordjevic AN, Andric NL, et al. Nitric oxide-scavenging activity of polyhydroxylated fullerenol, C60(OH)24. Nitric Oxide. 2004 Sep;11(2):201–7. DOI: 10.1016/j.niox.2004.08.003.Zha YY, Yang B, Tang ML, et al. Concentration- dependent effects of fullerenol on cultured hippocampal neuron viability. Int J Nanomedicine. 2012;7:3099–3109. DOI: 10.2147/IJN.S30934.Zha YY, Yang B, Tang ML, et al. Concentration- dependent effects of fullerenol on cultured hippocampal neuron viability. Int J Nanomedicine. 2012;7:3099–3109. DOI: 10.2147/IJN.S30934.Ye S, Chen M, Jiang Y, et al. Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system. Int J Nanomedicine. 2014;9:2073–2087. Published 2014 Apr 29. DOI: 10.2147/IJN.S56973.Ye S, Chen M, Jiang Y, et al. Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system. Int J Nanomedicine. 2014;9:2073–2087. Published 2014 Apr 29. DOI: 10.2147/IJN.S56973.Mrđanović J, Šolajić S, Bogdanović V, et al. Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutat Res Toxicol Environ Mutagen. 2009 Nov;680(1–2):25–30. DOI: 10.1016/j.mrgentox.2009.08.008.Mrđanović J, Šolajić S, Bogdanović V, et al. Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutat Res Toxicol Environ Mutagen. 2009 Nov;680(1–2):25–30. DOI: 10.1016/j.mrgentox.2009.08.008.Saitoh Y, Miyanishi A, Mizuno H, et al. Super- highly hydroxylated fullerene derivative protects human keratinocytes from UV-induced cell injuries together with the decreases in intracellular ROS generation and DNA damages. J Photochem Photobiol B. 2011;102(1):69–76. DOI: 10.1016/j.jphotobiol.2010.09.006.Saitoh Y, Miyanishi A, Mizuno H, et al. Super- highly hydroxylated fullerene derivative protects human keratinocytes from UV-induced cell injuries together with the decreases in intracellular ROS generation and DNA damages. J Photochem Photobiol B. 2011;102(1):69–76. DOI: 10.1016/j.jphotobiol.2010.09.006.Lu LH, Lee YT, Chen HW, et al. The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells. Br J Pharmacol. 1998;123(6):1097–1102. DOI: 10.1038/sj.bjp.0701722.Lu LH, Lee YT, Chen HW, et al. The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells. Br J Pharmacol. 1998;123(6):1097–1102. DOI: 10.1038/sj.bjp.0701722.Huang HC, Jan TR, Yeh SF. Inhibitory effect of curcumin, an anti-inflammatory agent, on vascular smooth muscle cell proliferation. Eur J Pharmacol. 1992;221(2– 3):381–384. DOI: 10.1016/0014-2999(92)90727-l.Huang HC, Jan TR, Yeh SF. Inhibitory effect of curcumin, an anti-inflammatory agent, on vascular smooth muscle cell proliferation. Eur J Pharmacol. 1992;221(2– 3):381–384. DOI: 10.1016/0014-2999(92)90727-l.Huang HC, Huang YL, Chang JH, et al. Possible mechanism of immunosuppressive effect of scoparone (6,7-dimethoxycoumarin). Eur J Pharmacol. 1992;217(2– 3):143–148. DOI: 10.1016/0014-2999(92)90835-r.Huang HC, Huang YL, Chang JH, et al. Possible mechanism of immunosuppressive effect of scoparone (6,7-dimethoxycoumarin). Eur J Pharmacol. 1992;217(2– 3):143–148. DOI: 10.1016/0014-2999(92)90835-r.Huang HC, Lee CR, Weng YI, et al. Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. Eur J Pharmacol. 1992;218(1):123–128. DOI: 10.1016/0014-2999(92)90155-w.Huang HC, Lee CR, Weng YI, et al. Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. Eur J Pharmacol. 1992;218(1):123–128. DOI: 10.1016/0014-2999(92)90155-w.Huang H-C, Hsieh L-M, Chen H-W, et al. Effects of baicalein and esculetin on transduction signals and growth factors expression in T-lymphoid leukemia cells. Eur J Pharmacol Mol Pharmacol. 1994 Jun;268(1):73–8. DOI: 10.1016/0922-4106(94)90121-X.Huang H-C, Hsieh L-M, Chen H-W, et al. Effects of baicalein and esculetin on transduction signals and growth factors expression in T-lymphoid leukemia cells. Eur J Pharmacol Mol Pharmacol. 1994 Jun;268(1):73–8. DOI: 10.1016/0922-4106(94)90121-X.Huang H-C, Lai M-W, Wang H-R, et al. Antiproliferative effect of esculetin on vascular smooth muscle cells: possible roles of signal transduction pathways. Eur J Pharmacol. 1993 Jun;237(1):39–44. DOI: 10.1016/0014-2999(93)90090-.Huang H-C, Lai M-W, Wang H-R, et al. Antiproliferative effect of esculetin on vascular smooth muscle cells: possible roles of signal transduction pathways. Eur J Pharmacol. 1993 Jun;237(1):39–44. DOI: 10.1016/0014-2999(93)90090-.Huang H-C, Wang H-R, Hsieh L-M. Antiproliferative effect of baicalein, a flavonoid from a Chinese herb, on vascular smooth muscle cell. Eur J Pharmacol. 1994 Jan;251(1):91–3. DOI: 10.1016/0014-2999(94)90447-2.Huang H-C, Wang H-R, Hsieh L-M. Antiproliferative effect of baicalein, a flavonoid from a Chinese herb, on vascular smooth muscle cell. Eur J Pharmacol. 1994 Jan;251(1):91–3. DOI: 10.1016/0014-2999(94)90447-2.Alvarez MG, Prucca C, Milanesio ME, et al. Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its biological consequences in a human carcinoma cell line. Int J Biochem Cell Biol. 2006;38(12):2092–2101. DOI: 10.1016/j.biocel.2006.05.019.Alvarez MG, Prucca C, Milanesio ME, et al. Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its biological consequences in a human carcinoma cell line. Int J Biochem Cell Biol. 2006;38(12):2092–2101. DOI: 10.1016/j.biocel.2006.05.019.Nakanishi I, Fukuzumi S, Konishi T, et al. DNA cleavage via electron transfer from NADH to molecular oxygen photosensitized by γ-cyclodextrin-bicapped C60. In: Fullerenes for the New Millennium. The Electrochemical Society, Inc., 2001. P. 138–51.Nakanishi I, Fukuzumi S, Konishi T, et al. DNA cleavage via electron transfer from NADH to molecular oxygen photosensitized by γ-cyclodextrin-bicapped C60. In: Fullerenes for the New Millennium. The Electrochemical Society, Inc., 2001. P. 138–51.Yamakoshi Y, Umezawa N, Ryu A, et al. Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2-* versus 1O2. J Am Chem Soc. 2003;125(42):12803–12809. DOI: 10.1021/ja0355574.Yamakoshi Y, Umezawa N, Ryu A, et al. Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2-* versus 1O2. J Am Chem Soc. 2003;125(42):12803–12809. DOI: 10.1021/ja0355574.Ikeda A, Doi Y, Hashizume M, et al. An Extremely Effective DNA Photocleavage Utilizing Functionalized Liposomes with a Fullerene-Enriched Lipid Bilayer. J Am Chem Soc. 2007 Apr 1;129(14):4140–1. DOI: 10.1021/ja070243s.Ikeda A, Doi Y, Hashizume M, et al. An Extremely Effective DNA Photocleavage Utilizing Functionalized Liposomes with a Fullerene-Enriched Lipid Bilayer. J Am Chem Soc. 2007 Apr 1;129(14):4140–1. DOI: 10.1021/ja070243s.Ikeda A, Hatano T, Kawaguchi M, et al. Water- soluble [60]fullerene–cationic homooxacalix[3]arene complex which is applicable to the photocleavage of DNA. Chem Commun. 1999;(15):1403–4. DOI: 10.1039/a903872h.Ikeda A, Hatano T, Kawaguchi M, et al. Water- soluble [60]fullerene–cationic homooxacalix[3]arene complex which is applicable to the photocleavage of DNA. Chem Commun. 1999;(15):1403–4. DOI: 10.1039/a903872h.Bernstein R, Prat F, Foote CS. On the Mechanism of DNA Cleavage by Fullerenes Investigated in Model Systems: Electron Transfer from Guanosine and 8-Oxo- Guanosine Derivatives to C 60. J Am Chem Soc. 1999 Jan 1;121(2):464–5. DOI: 10.1021/ja983335d.Bernstein R, Prat F, Foote CS. On the Mechanism of DNA Cleavage by Fullerenes Investigated in Model Systems: Electron Transfer from Guanosine and 8-Oxo- Guanosine Derivatives to C 60. J Am Chem Soc. 1999 Jan 1;121(2):464–5. DOI: 10.1021/ja983335d.Liu Y, Zhao Y-L, Chen Y, et al. A water-soluble β-cyclodextrin derivative possessing a fullerene tether as an efficient photodriven DNA-cleavage reagent. Tetrahedron Lett. 2005 Apr;46(14):2507–11. DOI: 10.1016/j.tetlet.2005.01.181.Liu Y, Zhao Y-L, Chen Y, et al. A water-soluble β-cyclodextrin derivative possessing a fullerene tether as an efficient photodriven DNA-cleavage reagent. Tetrahedron Lett. 2005 Apr;46(14):2507–11. DOI: 10.1016/j.tetlet.2005.01.181.Buchko GW, Wagner JR, Cadet J, et al. Methylene blue-mediated photooxidation of 7,8-dihydro-8-oxo-2′- deoxyguanosine. Biochim Biophys Acta - Gene Struct Expr. 1995;1263(1):17–24. DOI: https://doi.org/10.1016/0167-4781(95)00078-UBuchko GW, Wagner JR, Cadet J, et al. Methylene blue-mediated photooxidation of 7,8-dihydro-8-oxo-2′- deoxyguanosine. Biochim Biophys Acta - Gene Struct Expr. 1995;1263(1):17–24. DOI: https://doi.org/10.1016/0167-4781(95)00078-UDa Ros T, Spalluto G, Boutorine A, Prato M. Current Chemistry: Fullerene Derivatives as Potential DNA Photoprobes. Aust J Chem. 2001 Aug 6;54:223–4. DOI: 10.1071/CH01058.Da Ros T, Spalluto G, Boutorine A, Prato M. Current Chemistry: Fullerene Derivatives as Potential DNA Photoprobes. Aust J Chem. 2001 Aug 6;54:223–4. DOI: 10.1071/CH01058.Davies MJ. Singlet oxygen-mediated damage to proteins and its consequences. Biochem Biophys Res Commun. 2003;305(3):761–770. DOI: 10.1016/s0006-291x(03)00817-9.Davies MJ. Singlet oxygen-mediated damage to proteins and its consequences. Biochem Biophys Res Commun. 2003;305(3):761–770. DOI: 10.1016/s0006-291x(03)00817-9.Kamat JP, Devasagayam TPA, Priyadarsini KI, Mohan H. Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications. Toxicology. 2000;155(1):55–61. DOI: https://doi.org/10.1016/S0300-483X(00)00277-8Kamat JP, Devasagayam TPA, Priyadarsini KI, Mohan H. Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications. Toxicology. 2000;155(1):55–61. DOI: https://doi.org/10.1016/S0300-483X(00)00277-8Wang IC, Tai LA, Lee DD, et al. C 60 and Water- Soluble Fullerene Derivatives as Antioxidants Against Radical-Initiated Lipid Peroxidation. J Med Chem. 1999 Nov 1;42(22):4614–20. DOI: 10.1021/jm990144s.Wang IC, Tai LA, Lee DD, et al. C 60 and Water- Soluble Fullerene Derivatives as Antioxidants Against Radical-Initiated Lipid Peroxidation. J Med Chem. 1999 Nov 1;42(22):4614–20. DOI: 10.1021/jm990144s.Dugan LL, Turetsky DM, Du C, et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci U S A. 1997;94(17):9434–9439. DOI: 10.1073/pnas.94.17.9434.Dugan LL, Turetsky DM, Du C, et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci U S A. 1997;94(17):9434–9439. DOI: 10.1073/pnas.94.17.9434.Hu Z, Zhang C, Huang Y, et al. Photodynamic anticancer activities of water-soluble C(60) derivatives and their biological consequences in a HeLa cell line. Chem Biol Interact. 2012;195(1):86–94. DOI: 10.1016/j.cbi.2011.11.003.Hu Z, Zhang C, Huang Y, et al. Photodynamic anticancer activities of water-soluble C(60) derivatives and their biological consequences in a HeLa cell line. Chem Biol Interact. 2012;195(1):86–94. DOI: 10.1016/j.cbi.2011.11.003.Beuerle F, Witte P, Hartnagel U, et al. Cytoprotective activities of water-soluble fullerenes in zebrafish models. J Exp Nanosci. 2007 Sep 1;2(3):147–70. DOI: 10.1080/17458080701502091.Beuerle F, Witte P, Hartnagel U, et al. Cytoprotective activities of water-soluble fullerenes in zebrafish models. J Exp Nanosci. 2007 Sep 1;2(3):147–70. DOI: 10.1080/17458080701502091.Liu Z, Zou Y, Zhang Q, et al. Distinct Binding Dynamics, Sites and Interactions of Fullerene and Fullerenols with Amyloid-β Peptides Revealed by Molecular Dynamics Simulations. International Journal of Molecular Sciences. 2019; 20(8):2048. https://doi.org/10.3390/ijms20082048Liu Z, Zou Y, Zhang Q, et al. Distinct Binding Dynamics, Sites and Interactions of Fullerene and Fullerenols with Amyloid-β Peptides Revealed by Molecular Dynamics Simulations. International Journal of Molecular Sciences. 2019; 20(8):2048. https://doi.org/10.3390/ijms20082048Piotrovsky LB, Kiselev OI. Fullerenes and Viruses. Fullerenes, Nanotub Carbon Nanostructures. 2005 Jan 2;12(1–2):397–403. DOI: 10.1081/FST-120027198.Piotrovsky LB, Kiselev OI. Fullerenes and Viruses. Fullerenes, Nanotub Carbon Nanostructures. 2005 Jan 2;12(1–2):397–403. DOI: 10.1081/FST-120027198.Burley GA, Keller PA, Pyne SG. [60] Fullerene Amino Acids and Related Derivatives, Fullerene Science and Technology. 1999;7:6, 973–1001. DOI: 10.1080/10641229909350301.Burley GA, Keller PA, Pyne SG. [60] Fullerene Amino Acids and Related Derivatives, Fullerene Science and Technology. 1999;7:6, 973–1001. DOI: 10.1080/10641229909350301.Bianco A, Da Ros T, Prato M, Toniolo C. Fullerene-based amino acids and peptides. J Pept Sci. 2001;7(4):208– 219. DOI: 10.1002/psc.313.Bianco A, Da Ros T, Prato M, Toniolo C. Fullerene-based amino acids and peptides. J Pept Sci. 2001;7(4):208– 219. DOI: 10.1002/psc.313.Bjelaković M, Kop T, Maslak V, et al. Synthesis and characterization of highly ordered self-assembled bioactive fulleropeptides. J Mater Sci. 2016; 51:739–747. DOI: 10.1007/s10853-015-9396-z.Bjelaković M, Kop T, Maslak V, et al. Synthesis and characterization of highly ordered self-assembled bioactive fulleropeptides. J Mater Sci. 2016; 51:739–747. DOI: 10.1007/s10853-015-9396-z.Huang HM, Ou HC, Hsieh SJ, Chiang LY. Blockage of amyloid beta peptide-induced cytosolic free calcium by fullerenol-1, carboxylate C60 in PC12 cells. Life Sci. 2000;66(16):1525–1533. DOI: 10.1016/s0024-3205(00)00470-7.Huang HM, Ou HC, Hsieh SJ, Chiang LY. Blockage of amyloid beta peptide-induced cytosolic free calcium by fullerenol-1, carboxylate C60 in PC12 cells. Life Sci. 2000;66(16):1525–1533. DOI: 10.1016/s0024-3205(00)00470-7.Basso AS, Frenkel D, Quintana FJ, et al. Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest. 2008;118(4):1532–1543. DOI: 10.1172/JCI33464.Basso AS, Frenkel D, Quintana FJ, et al. Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest. 2008;118(4):1532–1543. DOI: 10.1172/JCI33464.Ali SS, Hardt JI, Dugan LL. SOD activity of carboxyfullerenes predicts their neuroprotective efficacy: a structure-activity study. Nanomedicine. 2008;4(4):283– 294. DOI: 10.1016/j.nano.2008.05.003.Ali SS, Hardt JI, Dugan LL. SOD activity of carboxyfullerenes predicts their neuroprotective efficacy: a structure-activity study. Nanomedicine. 2008;4(4):283– 294. DOI: 10.1016/j.nano.2008.05.003.Dugan LL, Tian L, Quick KL, et al. Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates. Ann Neurol. 2014;76(3):393–402. DOI: 10.1002/ana.24220.Dugan LL, Tian L, Quick KL, et al. Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates. Ann Neurol. 2014;76(3):393–402. DOI: 10.1002/ana.24220.Moussa F, Chretie P, Dubois P, et al. The Influence of C 60 Powders On Cultured Human Leukocytes. Fuller Sci Technol. 1995 Jan;3(3):333–42. DOI: 10.1080/153638X9508543788.Moussa F, Chretie P, Dubois P, et al. The Influence of C 60 Powders On Cultured Human Leukocytes. Fuller Sci Technol. 1995 Jan;3(3):333–42. DOI: 10.1080/153638X9508543788.Moussa F, Trivin F, Céolin R, et al. Early effects of C60 Administration in Swiss Mice: A Preliminary Account for In Vivo C60 Toxicity. Fullerene Science and Technology. 1996;4(1):21–29. DOI: 10.1080/10641229608001534.Moussa F, Trivin F, Céolin R, et al. Early effects of C60 Administration in Swiss Mice: A Preliminary Account for In Vivo C60 Toxicity. Fullerene Science and Technology. 1996;4(1):21–29. DOI: 10.1080/10641229608001534.Piotrovskii LB. Fullerenes in the drug design. Nanotechnol Russia. 2009;4:541–555. https://doi. org/10.1134/S1995078009090018Piotrovskii LB. Fullerenes in the drug design. Nanotechnol Russia. 2009;4:541–555. https://doi. org/10.1134/S1995078009090018Hendrickson OD, Morozova OV, Zherdev AV, et al. Study of Distribution and Biological Effects of Fullerene C60 after Single and Multiple Intragastrical Administrations to Rats, Fullerenes, Nanotubes and Carbon Nanostructures. 2015;23(7):658–668. DOI: 10.1080/1536383X.2014.949695.Hendrickson OD, Morozova OV, Zherdev AV, et al. Study of Distribution and Biological Effects of Fullerene C60 after Single and Multiple Intragastrical Administrations to Rats, Fullerenes, Nanotubes and Carbon Nanostructures. 2015;23(7):658–668. DOI: 10.1080/1536383X.2014.949695.Gao J, Wang HL, Shreve A, Iyer R. Fullerene derivatives induce premature senescence: a new toxicity paradigm or novel biomedical applications. Toxicol Appl Pharmacol. 2010;244(2):130–143. DOI: 10.1016/j. taap.2009.12.025.Gao J, Wang HL, Shreve A, Iyer R. Fullerene derivatives induce premature senescence: a new toxicity paradigm or novel biomedical applications. Toxicol Appl Pharmacol. 2010;244(2):130–143. DOI: 10.1016/j. taap.2009.12.025.Trpkovic A, Todorovic-Markovic B, Trajkovic V. Toxicity of pristine versus functionalized fullerenes: mechanisms of cell damage and the role of oxidative stress. Arch Toxicol. 2012;86(12):1809–1827. DOI: 10.1007/ s00204-012-0859-6.Trpkovic A, Todorovic-Markovic B, Trajkovic V. Toxicity of pristine versus functionalized fullerenes: mechanisms of cell damage and the role of oxidative stress. Arch Toxicol. 2012;86(12):1809–1827. DOI: 10.1007/ s00204-012-0859-6.Andrievsky G, Klochkov V, Derevyanchenko L. Is the C60 Fullerene Molecule Toxic, Fullerenes, Nanotubes and Carbon Nanostructures. 2005;13(4):363–376. DOI: 10.1080/15363830500237267.Andrievsky G, Klochkov V, Derevyanchenko L. Is the C60 Fullerene Molecule Toxic, Fullerenes, Nanotubes and Carbon Nanostructures. 2005;13(4):363–376. DOI: 10.1080/15363830500237267.Baati T, Bourasset F, Gharbi N, et al. The prolongation of the lifespan of rats by repeated oral administration of fullerene [published correction appears in Biomaterials. 2012 Sep;33(26):6292–4]. Biomaterials. 2012;33(19):4936–4946. DOI: 10.1016/j. biomaterials.2012.03.036.Baati T, Bourasset F, Gharbi N, et al. The prolongation of the lifespan of rats by repeated oral administration of fullerene [published correction appears in Biomaterials. 2012 Sep;33(26):6292–4]. Biomaterials. 2012;33(19):4936–4946. DOI: 10.1016/j. biomaterials.2012.03.036.Xu J-Y, Su Y-Y, Cheng J-S, et al. Protective effects of fullerenol on carbon tetrachloride-induced acute hepatotoxicity and nephrotoxicity in rats. Carbon N Y. 2010;48(5):1388–96. DOI: https://doi.org/10.1016/j.carbon.2009.12.029.Xu J-Y, Su Y-Y, Cheng J-S, et al. Protective effects of fullerenol on carbon tetrachloride-induced acute hepatotoxicity and nephrotoxicity in rats. Carbon N Y. 2010;48(5):1388–96. DOI: https://doi.org/10.1016/j.carbon.2009.12.029.Slavic M, Djordjevic A, Radojicic R, et al. Fullerenol C60(OH)24 nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction. J Nanopart Res 15, 1650 (2013). https://doi.org/10.1007/s11051-013-1650-1Slavic M, Djordjevic A, Radojicic R, et al. Fullerenol C60(OH)24 nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction. J Nanopart Res 15, 1650 (2013). https://doi.org/10.1007/s11051-013-1650-1Isakovic A, Markovic Z, Todorovic-Markovic B, et al. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol Sci. 2006;91(1):173–183. DOI: 10.1093/toxsci/kfj127.Isakovic A, Markovic Z, Todorovic-Markovic B, et al. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol Sci. 2006;91(1):173–183. DOI: 10.1093/toxsci/kfj127.Injac R, Perse M, Boskovic M, et al. Cardioprotective effects of fullerenol C(60) (Oh)(24) on a single dose doxorubicin-induced cardiotoxicity in rats with malignant neoplasm. Technol Cancer Res Treat. 2008;7(1):15–25. DOI: 10.1177/153303460800700102.Injac R, Perse M, Boskovic M, et al. Cardioprotective effects of fullerenol C(60) (Oh)(24) on a single dose doxorubicin-induced cardiotoxicity in rats with malignant neoplasm. Technol Cancer Res Treat. 2008;7(1):15–25. DOI: 10.1177/153303460800700102.Djordjević-Milić V, Djordjević A, Dobrić S, et al. Influence of Fullerenol C60(OH)24 on Doxorubicin Induced Cardiotoxicity in Rats. Mater Sci Forum. 2006 Jul; 518:525– 30. DOI: 10.4028/www.scientific.net/MSF.518.525.Djordjević-Milić V, Djordjević A, Dobrić S, et al. Influence of Fullerenol C60(OH)24 on Doxorubicin Induced Cardiotoxicity in Rats. Mater Sci Forum. 2006 Jul; 518:525– 30. DOI: 10.4028/www.scientific.net/MSF.518.525.Injac R, Boskovic M, Perse M, et al. Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress. Pharmacol Rep. 2008;60(5):742–749.Injac R, Boskovic M, Perse M, et al. Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress. Pharmacol Rep. 2008;60(5):742–749.Injac R, Perse M, Obermajer N, et al. Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas. Biomaterials. 2008;29(24–25):3451–3460. DOI: 10.1016/j.biomaterials.2008.04.048.Injac R, Perse M, Obermajer N, et al. Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas. Biomaterials. 2008;29(24–25):3451–3460. DOI: 10.1016/j.biomaterials.2008.04.048.Saathoff JG, Inman AO, Xia XR, et al. In vitro toxicity assessment of three hydroxylated fullerenes in human skin cells. Toxicol In Vitro. 2011;25(8):2105–2112. DOI: 10.1016/j.tiv.2011.09.013.Saathoff JG, Inman AO, Xia XR, et al. In vitro toxicity assessment of three hydroxylated fullerenes in human skin cells. Toxicol In Vitro. 2011;25(8):2105–2112. DOI: 10.1016/j.tiv.2011.09.013.Xu D, Liu M, Huang Q, et al. A Novel method for the preparation of fluorescent C60 poly(amino acid) composites and their biological imaging. J Colloid Interface Sci. 2018;516:392–397. DOI: 10.1016/j.jcis.2018.01.085.Xu D, Liu M, Huang Q, et al. A Novel method for the preparation of fluorescent C60 poly(amino acid) composites and their biological imaging. J Colloid Interface Sci. 2018;516:392–397. DOI: 10.1016/j.jcis.2018.01.085.Rouse JG, Yang J, Barron AR, Monteiro-Riviere NA. Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes. Toxicol In Vitro. 2006;20(8):1313–1320. DOI: 10.1016/j.tiv.2006.04.004.Rouse JG, Yang J, Barron AR, Monteiro-Riviere NA. Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes. Toxicol In Vitro. 2006;20(8):1313–1320. DOI: 10.1016/j.tiv.2006.04.004.Lucafò M, Pacor S, Fabbro C, et al. Study of a potential drug delivery system based on carbon nanoparticles: effects of fullerene derivatives in MCF7 mammary carcinoma cells. J Nanoparticle Res. 2012 Mar 28;14(4):830. DOI: 10.1007/s11051-012-0830-8.Lucafò M, Pacor S, Fabbro C, et al. Study of a potential drug delivery system based on carbon nanoparticles: effects of fullerene derivatives in MCF7 mammary carcinoma cells. J Nanoparticle Res. 2012 Mar 28;14(4):830. DOI: 10.1007/s11051-012-0830-8.Chen M, Qin X, Zeng G. Biodegradation of Carbon Nanotubes, Graphene, and Their Derivatives. Trends Biotechnol. 2017;35(9):836–846. DOI: 10.1016/j.tibtech.2016.12.001.Chen M, Qin X, Zeng G. Biodegradation of Carbon Nanotubes, Graphene, and Their Derivatives. Trends Biotechnol. 2017;35(9):836–846. DOI: 10.1016/j.tibtech.2016.12.001.Allen BL, Kotchey GP, Chen Y, et al. Mechanistic Investigations of Horseradish Peroxidase-Catalyzed Degra- dation of Single-Walled Carbon Nanotubes. J Am Chem Soc. 2009 Dec 2;131(47):17194–205. DOI: 10.1021/ja9083623.Allen BL, Kotchey GP, Chen Y, et al. Mechanistic Investigations of Horseradish Peroxidase-Catalyzed Degra- dation of Single-Walled Carbon Nanotubes. J Am Chem Soc. 2009 Dec 2;131(47):17194–205. DOI: 10.1021/ja9083623.Kagan VE, Kapralov AA, St Croix CM, et al. Lung macrophages “digest” carbon nanotubes using a superoxide/peroxynitrite oxidative pathway. ACS Nano. 2014;8(6):5610–5621. DOI: 10.1021/nn406484b.Kagan VE, Kapralov AA, St Croix CM, et al. Lung macrophages “digest” carbon nanotubes using a superoxide/peroxynitrite oxidative pathway. ACS Nano. 2014;8(6):5610–5621. DOI: 10.1021/nn406484b.Li D, Fortner JD, Johnson DR, et al. Bioaccumulation of 14C60 by the Earthworm Eisenia fetida. Environ Sci Technol. 2010 Dec 1;44(23):9170–5. DOI: 10.1021/es1024405.Li D, Fortner JD, Johnson DR, et al. Bioaccumulation of 14C60 by the Earthworm Eisenia fetida. Environ Sci Technol. 2010 Dec 1;44(23):9170–5. DOI: 10.1021/es1024405.Avanasi R, Jackson WA, Sherwin B, et al. C60 Fullerene Soil Sorption, Biodegradation, and Plant Uptake. Environ Sci Technol. 2014 Mar 4;48(5):2792–7. DOI: 10.1021/es405306w.Avanasi R, Jackson WA, Sherwin B, et al. C60 Fullerene Soil Sorption, Biodegradation, and Plant Uptake. Environ Sci Technol. 2014 Mar 4;48(5):2792–7. DOI: 10.1021/es405306w.Navarro DA, Kookana RS, McLaughlin MJ, Kirby JK. Fate of radiolabeled C60 fullerenes in aged soils. Environ Pollut. 2017 Feb;221:293–300. DOI: 10.1016/j.envpol.2016.11.077.Navarro DA, Kookana RS, McLaughlin MJ, Kirby JK. Fate of radiolabeled C60 fullerenes in aged soils. Environ Pollut. 2017 Feb;221:293–300. DOI: 10.1016/j.envpol.2016.11.077.Berry TD, Filley TR, Clavijo AP, et al. Degradation and Microbial Uptake of C60 Fullerols in Contrasting Agricultural Soils. Environ Sci Technol. 2017 Feb 7;51(3):1387–94. DOI: 10.1021/acs.est.6b04637.Berry TD, Filley TR, Clavijo AP, et al. Degradation and Microbial Uptake of C60 Fullerols in Contrasting Agricultural Soils. Environ Sci Technol. 2017 Feb 7;51(3):1387–94. DOI: 10.1021/acs.est.6b04637.Navarro DA, Kookana RS, McLaughlin MJ, et al. Fullerol as a Potential Pathway for Mineralization of Fullerene Nanoparticles in Biosolid-Amended Soils. Environ Sci Technol Lett. 2016 Jan 12;3(1):7–12. DOI: 10.1021/acs.estlett.5b00292.Navarro DA, Kookana RS, McLaughlin MJ, et al. Fullerol as a Potential Pathway for Mineralization of Fullerene Nanoparticles in Biosolid-Amended Soils. Environ Sci Technol Lett. 2016 Jan 12;3(1):7–12. DOI: 10.1021/acs.estlett.5b00292.Tiwari AJ, Morris JR, Vejerano EP, et al. Oxidation of c60 aerosols by atmospherically relevant levels of o3. Environ Sci Technol. 2014;48(5):2706–2714. DOI: 10.1021/es4045693.Tiwari AJ, Morris JR, Vejerano EP, et al. Oxidation of c60 aerosols by atmospherically relevant levels of o3. Environ Sci Technol. 2014;48(5):2706–2714. DOI: 10.1021/es4045693.Fortner JD, Kim D-I, Boyd AM, et al. Reaction of Water-Stable C60 Aggregates with Ozone. Environ Sci Technol. 2007 Nov 1;41(21):7497–502. DOI: 10.1021/es0708058.Fortner JD, Kim D-I, Boyd AM, et al. Reaction of Water-Stable C60 Aggregates with Ozone. Environ Sci Technol. 2007 Nov 1;41(21):7497–502. DOI: 10.1021/es0708058.Sanchís J, Aminot Y, Abad E, et al. Transformation of C60 fullerene aggregates suspended and weathered under realistic environmental conditions. Carbon N Y. 2018 Mar;128:54–62. DOI: 10.1016/j.carbon.2017.11.060.Sanchís J, Aminot Y, Abad E, et al. Transformation of C60 fullerene aggregates suspended and weathered under realistic environmental conditions. Carbon N Y. 2018 Mar;128:54–62. DOI: 10.1016/j.carbon.2017.11.060.Gitsov I, Simonyan A, Wang L, et al. Polymer- assisted biocatalysis: Unprecedented enzymatic oxidation of fullerene in aqueous medium. J Polym Sci Part A Polym Chem. 2012 Jan 23;50(1):119–26. DOI: 10.1002/pola.24995.Gitsov I, Simonyan A, Wang L, et al. Polymer- assisted biocatalysis: Unprecedented enzymatic oxidation of fullerene in aqueous medium. J Polym Sci Part A Polym Chem. 2012 Jan 23;50(1):119–26. DOI: 10.1002/pola.24995.Litasova EV, Iljin VV, Sokolov AV, et al. The biodegradation of fullerene C60 by myeloperoxidase. Dokl Biochem Biophys. 2016;471(1):417–420. DOI: 10.1134/S1607672916060119.Litasova EV, Iljin VV, Sokolov AV, et al. The biodegradation of fullerene C60 by myeloperoxidase. Dokl Biochem Biophys. 2016;471(1):417–420. DOI: 10.1134/S1607672916060119.Brant JA, Labille J, Bottero JY, Wiesner MR. Characterizing the impact of preparation method on fullerene cluster structure and chemistry. Langmuir. 2006;22(8):3878–3885. DOI: 10.1021/la053293o.Brant JA, Labille J, Bottero JY, Wiesner MR. Characterizing the impact of preparation method on fullerene cluster structure and chemistry. Langmuir. 2006;22(8):3878–3885. DOI: 10.1021/la053293o.Li T, Zhang C-Z, Fan X, et al. Degradation of oxidized multi-walled carbon nanotubes in water via photo- Fenton method and its degradation mechanism. Chem Eng J. 2017 Sep;323:37–46. DOI: 10.1016/j.cej.2017.04.081.Li T, Zhang C-Z, Fan X, et al. Degradation of oxidized multi-walled carbon nanotubes in water via photo- Fenton method and its degradation mechanism. Chem Eng J. 2017 Sep;323:37–46. DOI: 10.1016/j.cej.2017.04.081.Li T, Zhang C-Z, Ding D, et al. Experimental and theoretical study on degradation of oxidized C60 in water via photo-Fenton method. Chem Eng J. 2018 Feb;334:587– 97. DOI: 10.1016/j.cej.2017.10.062.Li T, Zhang C-Z, Ding D, et al. Experimental and theoretical study on degradation of oxidized C60 in water via photo-Fenton method. Chem Eng J. 2018 Feb;334:587– 97. DOI: 10.1016/j.cej.2017.10.062.Trajković S, Dobrić S, Jaćević V, et al. Tissue- protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloids Surf B Biointerfaces. 2007;58(1):39–43. DOI: 10.1016/j.colsurfb.2007.01.005.Trajković S, Dobrić S, Jaćević V, et al. Tissue- protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloids Surf B Biointerfaces. 2007;58(1):39–43. DOI: 10.1016/j.colsurfb.2007.01.005.Grebowski J, Kazmierska P, Litwinienko G, et al. Fullerenol C60(OH)36 protects human erythrocyte membrane against high-energy electrons. Biochim Biophys Acta Biomembr. 2018;1860(8):1528–1536. DOI: 10.1016/j.bbamem.2018.05.005.Grebowski J, Kazmierska P, Litwinienko G, et al. Fullerenol C60(OH)36 protects human erythrocyte membrane against high-energy electrons. Biochim Biophys Acta Biomembr. 2018;1860(8):1528–1536. DOI: 10.1016/j.bbamem.2018.05.005.Орлова М.А., Трофимова Т.П., Орлов А.П. и др. Фуллерены и апоптоз. Онкогематология. 2013;8(1):65–71. DOI: 10.17650/1818-8346-2013-8-1-65-71.Orlova MA, Trofimova TP, Orlov AP, et al. Fullerene and apoptosis. Oncohematology. 2013;8(1):65– 71. In Russian. DOI: 10.17650/1818-8346-2013-8-1-65-71.Mroz P, Tegos GP, Gali H, et al. Photodynamic therapy with fullerenes. Photochem Photobiol Sci. 2007;6(11):1139–1149. DOI: 10.1039/b711141j.Mroz P, Tegos GP, Gali H, et al. Photodynamic therapy with fullerenes. Photochem Photobiol Sci. 2007;6(11):1139–1149. DOI: 10.1039/b711141j.Jiang G, Yin F, Duan J, Li G. Synthesis and properties of novel water-soluble fullerene-glycine derivatives as new materials for cancer therapy. J Mater Sci Mater Med. 2015;26(1):5348. DOI: 10.1007/s10856-014-5348-4.Jiang G, Yin F, Duan J, Li G. Synthesis and properties of novel water-soluble fullerene-glycine derivatives as new materials for cancer therapy. J Mater Sci Mater Med. 2015;26(1):5348. DOI: 10.1007/s10856-014-5348-4.Piotrovskiy LB, Litasova EV, Dumpis MA, et al. Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C60. Dokl Biochem Biophys. 2016;468(1):173–175. DOI: 10.1134/S1607672916030030.Piotrovskiy LB, Litasova EV, Dumpis MA, et al. Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C60. Dokl Biochem Biophys. 2016;468(1):173–175. DOI: 10.1134/S1607672916030030.Hsieh FY, Zhilenkov AV, Voronov II, et al. Water- Soluble Fullerene Derivatives as Brain Medicine: Surface Chemistry Determines If They Are Neuroprotective and Antitumor. ACS Appl Mater Interfaces. 2017;9(13):11482– 11492. DOI: 10.1021/acsami.7b01077.Hsieh FY, Zhilenkov AV, Voronov II, et al. Water- Soluble Fullerene Derivatives as Brain Medicine: Surface Chemistry Determines If They Are Neuroprotective and Antitumor. ACS Appl Mater Interfaces. 2017;9(13):11482– 11492. DOI: 10.1021/acsami.7b01077.Rezayat SM, Boushehri SV, Salmanian B, et al. The porphyrin-fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect. Eur J Med Chem. 2009;44(4):1554–1569. DOI: 10.1016/j.ejmech.2008.07.030.Rezayat SM, Boushehri SV, Salmanian B, et al. The porphyrin-fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect. Eur J Med Chem. 2009;44(4):1554–1569. DOI: 10.1016/j.ejmech.2008.07.030.Amirshahi N, Alyautdin RN, Sarkar S, et al. Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle. Arch Med Res. 2008;39(6):549–559. DOI: 10.1016/j.arcmed.2008.05.007.Amirshahi N, Alyautdin RN, Sarkar S, et al. Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle. Arch Med Res. 2008;39(6):549–559. DOI: 10.1016/j.arcmed.2008.05.007.

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