ISSN 0869-6632 (Print)
ISSN 2542-1905 (Online)


For citation:

Gulyaev Y. V., Cherepenin V. A., Taranov I. V., Vdovin V. A., Yaroslavov A. A., Kravtsov I. D., Grigoryan I. V., Koksharov Y. A., Khomutov G. B. Changes of the structure and permeability of lipid membranes caused by nanoparticles and pulsed electromagnetic effects. Izvestiya VUZ. Applied Nonlinear Dynamics, 2025, vol. 33, iss. 5, pp. 709-730. DOI: 10.18500/0869-6632-003184, EDN: AIMACM

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).
Full text PDF(Ru):
Full text PDF(En):
Language: 
Russian
Article type: 
Article
UDC: 
530.182
EDN: 

Changes of the structure and permeability of lipid membranes caused by nanoparticles and pulsed electromagnetic effects

Autors: 
Gulyaev Yuri Vasilyevich, Kotel'nikov Institute of Radioengineering and Electronics of Russian Academy of Sciences
Cherepenin Vladimir Alekseevich, Kotel'nikov Institute of Radioengineering and Electronics of Russian Academy of Sciences
Taranov Igor Vladimirovich, Kotel'nikov Institute of Radioengineering and Electronics of Russian Academy of Sciences
Vdovin Vladimir Aleksandrovich, Kotel'nikov Institute of Radioengineering and Electronics of Russian Academy of Sciences
Yaroslavov Alexander Anatolyevich, Lomonosov Moscow State University
Kravtsov Igor Dmitrievich, Fryazino Branch of Kotel`nikov Institute of Radiophysics and Electronics of Russian Academy of Sciences
Grigoryan Ilya Valentinovich, Lomonosov Moscow State University
Koksharov Yury Alexeevich, Lomonosov Moscow State University
Khomutov Gennadii Borisovich, Lomonosov Moscow State University
Abstract: 

The work is devoted to the development of effective and safe biocompatible means and methods of encapsulation, targeted delivery and controlled release of drugs in aqueous environments, including living systems. For encapsulation of medicinal compounds in colloidal carriers, originally created nanostructured biomimetic lipid membrane vesicles were used - nanocomposite liposomes, the membranes of which are functionalized with magnetite and gold nanoparticles. To solve the problem of safe controlled release of an encapsulated substance into aqueous media, an approach has been developed based on the use of powerful ultrashort electrical pulses with a duration of less than 10 ns, providing a non-thermal effect of selective controlled electroporation of nanocomposite lipid membranes containing conductive nanoparticles. A theoretical model of non-thermal interaction of nanostructured liposomal capsules with ultrashort electrical pulses has been developed, within the framework of which an expression has been obtained for the critical value of the electric field strength that determines the threshold for the occurrence of the electroporation effect in a conducting aqueous medium. The key role of electrically conductive nanoparticles in increasing the sensitivity of the structure and conductivity of nanocomposite liposomes to external ultrashort electric sunlight is shown. The theoretically described mechanism of change in the structure and conductivity of lipid membranes containing electrically conductive nanoparticles explains the selective controlled nature of ultrashort pulse action on nanocomposite liposomal containers. The effect of controlled selective change in permeability and decapsulation of nanocomposite liposomes was registered by fluorimetry methods in experiments with the anticancer antibiotic doxorubicin and the fluorescent dye carboxyfluorescein, which were loaded into liposomal carriers as model molecular compounds. Encapsulated substances were released from nanocomposite liposomes after exposure to ultrashort electrical pulses with an efficiency of up to 98%, while no significant changes in the structural and functional state of natural and pure lipid membranes were recorded. The data on changes in membrane permeability correlated well with the results on structural changes in nanocomposite liposomes recorded by transmission electron microscopy and atomic force microscopy.
 

Acknowledgments: 
The work was carried out within the framework of the state assignment (FFWZ-2025-0013).
Reference: 
  1. Tewabe A, Abate A, Tamrie M, Seyfu A, Abdela Siraj E.. Targeted drug delivery — from magic bullet to nanomedicine: Principles, challenges, and future perspectives. J. Multidiscip. Healthc. 2021;14:1711–1724. DOI: 10.2147/JMDH.S313968.
  2. Vargason AM, Anselmo AC, Mitragotri S. The evolution of commercial drug delivery technologies. Nat. Biomed. Eng. 2021;5(9):951–967. DOI: 10.1038/s41551-021-00698-w.
  3. Ezikea TC, Okpalaa US, Lovet OU, Nwikea CP, Ezeakoa EC, Okparaa OJ, Okoroafora CC, Ezec SC, Kaluc OL, Odohd EC, Nwadikea UG, Ogbodoa JO, Umehb BU, Ossaia EC, Nwanguma BC. Advances in drug delivery systems, challenges and future directions. Heliyon. 2023;9(6): e17488. DOI: 10.1016/j.heliyon.2023.e17488.
  4. Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, Bannerjee SK. Drug delivery systems: An updated review. Int. J. Pharm. Investig. 2012;2(1):2–11. DOI: 10.4103/2230- 973X.96920.
  5. Bhagwat RR, Vaidhya IS. Novel drug delivery systems: an overview. Int. J. Pharm. Sci. Res. 2013;4(3):970–982. DOI: 10.13040/IJPSR.0975-8232.4(3).970-82.
  6. Muller-Goymann CC. Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration. Eur. J. Pharm. Biopharm. 2004;58(2):343–356. DOI: 10.1016/j.ejpb.2004.03.028.
  7. Maximchik PV, Tamarov K, Sheval EV, Tolstik E, Kirchberger-Tolstik T, Yang Z, Sivakov V, Zhivotovsky B, Osminkina LA. Biodegradable porous silicon nanocontainers as an effective drug carrier for regulation of the tumor cell death pathways. ACS Biomater. Sci. Eng. 2019;5(11): 6063–6071. DOI: 10.1021/acsbiomaterials.9b01292.
  8. Khurana S, Jain NK, Bedi PMS. Development and characterization of a novel controlled release drug delivery system based on nanostructured lipid carriers gel for meloxicam. Life Sci. 2013;93(21):763–772. DOI: 10.1016/j.lfs.2013.09.027.
  9. Xiong W, Li L, Wang Y, Yu Y, Wang S, Gao Y, Liang Y, Zhang G, Pan W, Yang X. Design and evaluation of a novel potential carrier for a hydrophilic antitumor drug: Auricularia auricular polysaccharide-chitosan nanoparticles as a delivery system for doxorubicin hydrochloride. Int. J. Pharm. 2016;511(1):267–275. DOI: 10.1016/j.ijpharm.2016.07.026.
  10.  Sessa G, Weissmann G. Phospholipid spherules (liposomes) as a model for biological membranes. J. Lipid Res. 1968;9(3):310–318. DOI: 10.1016/S0022-2275(20)43097-4.
  11.  Lasic DD. Liposomes: From Physics to Applications. Amsterdam: Elsevier; 1993. 580 p.
  12.  Torchilin V, Weissig V, editors. Liposomes: A Practical Approach. Oxford: Oxford University Press; 2003. 396 p.
  13.  Schwendener RA. Liposomes in biology and medicine. In: Chan WCW, editor. Bio-Applications of Nanoparticles. Advances in Experimental Medicine and Biology. Vol. 620. NY: Springer; 2007. P. 117–128. DOI: 10.1007/978-0-387-76713-0_9.
  14.  Liu P, Chen G, Zhang J. A review of liposomes as a drug delivery system: current status of approved products, regulatory environments, and future perspectives. Molecules. 2022;27(4):1372. DOI: 10.3390/molecules27041372.
  15.  Koksharov YA, Gubin SP, Taranov IV, Khomutov GB, Gulyaev YV. Magnetic nanoparticles in medicine: progress, problems, and advances. J. Commun. Technol. Electron. 2022;67(2):101–116. DOI: 10.1134/S1064226922020073.
  16.  Veiseh O., Gunn J. W., Zhang M. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv. Drug. Deliv. Rev. 2010;62(3):284–304. DOI: 10.1016/j.addr.2009. 11.002.
  17.  Neuberger T, Schopf B, Hofmann H, Hofmann M, Von Rechenberg B. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system. J. Magn. Magn. Mater. 2005;293(1):483–496. DOI: 10.1016/j.jmmm.2005.01.064.
  18.  Nasongkla N, Bey E, Ren J, Ai H, Khemtong C, Guthi JS, Chin S-F, Sherry AD, Boothman DA, Gao J. Multifunctional polymeric micelles as cancer-targeted. Nano Lett. 2006;6(11):2427–2430. DOI: 10.1021/nl061412u.
  19.  Berezin MY, editor. Nanotechnology for Biomedical Imaging and Diagnostics: From Nanoparticle Design to Clinical Applications. New York: Wiley; 2015. 520 p. DOI: 10.1002/9781118873151.
  20.  Gubin SP, Koksharov YA, Khomutov GB, Yurkov GY. Magnetic nanoparticles: preparation, structure and properties. Russ. Chem. Rev. 2005;74(6):489–520. DOI: 10.1070/rc2005v074n06 abeh000897.
  21.  Amstad E, Textor M, Reimhult E. Stabilization and functionalization of iron oxide nanoparticles for biomedical applications. Nanoscale. 2011;3(7):2819–2843. DOI: 10.1039/C1NR10173K.
  22.  Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 2005;26(18):3995–4021. DOI: 10.1016/j.biomaterials.2004.10.012.
  23.  Berry CC, Curtis AS. Functionalisation of magnetic nanoparticles for applications in biomedicine. J. Phys. D: Appl. Phys. 2005;36(13):R198-R206. DOI: 10.1088/0022-3727/36/13/203.
  24.  Akbarzadeh A, Samiei M, Davaran S. Magnetic nanoparticles: preparation, physical properties, and applications in biomedicine. Nanoscale Res. Lett. 2012;7:144. DOI: 10.1186/1556-276X-7-144.
  25.  Huang Y, Hsu JC, Koo H, Cormode DP. Repurposing ferumoxytol: Diagnostic and therapeutic applications of an FDA-approved nanoparticle. Theranostics. 2022;12(2):796–816. DOI: 10.7150/ thno.67375.
  26.  Amstad E, Kohlbrecher J, Muller E, Schweizer T, Textor M, Reimhult E. Triggered release from liposomes through magnetic actuation of iron oxide nanoparticle containing membranes. Nano Lett. 2011;11(4):1664–1670. DOI: 10.1021/nl2001499.
  27.  Vlasova KY, Piroyan A, Le-Deygen IM, Vishwasrao HM, Ramsey JD, Klyachko NL, Golovin YI, Rudakovskaya PG, Kireev II, Kabanov AV, Sokolsky-Papkov M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications Magnetic liposome design for drug release systems responsive to super-low frequency alternating current magnetic field (AC MF). J. Colloid Interface Sci. 2019;552:689–700. DOI: 10.1016/j.jcis.2019.05.071.
  28.  Khomutov GB, Kim VP, Koksharov YuA, Potapenkov KV, Parshintsev AA, Soldatov ES, Usmanov NN, Saletsky AM, Sybachin AV, Yaroslavov AA, Taranov IV, Cherepenin VA, Gulyaev YV. Nanocomposite biomimetic vesicles based on interfacial complexes of polyelectrolytes and colloid magnetic nanoparticles. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2017;532:26–35. DOI: 10.1016/j.colsurfa.2017.07.035.
  29.  Nguyen TT. Gold nanoparticles for targeting of biomedical applications: A review. Asian Journal of Chemistry. 2024;36(8):1741–1746. DOI: 10.14233/ajchem.2024.31729.
  30.  Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA. The golden age: gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012;41(7):2740–2779. DOI: 10.1039/C1CS15237H.
  31.  Kumalasari MR, Alfanaar R, Andreani AS. Gold nanoparticles (AuNPs): A versatile material for biosensor application. Talanta Open. 2024;9:100327. DOI: 10.1016/j.talo.2024.100327.
  32.  Ferrari E. Gold nanoparticle-based plasmonic biosensors. Biosensors. 2023;13(3):411. DOI: 10. 3390/bios13030411.
  33.  Goddard ZR, Beekman AM, Cominetti MMD, O’Connell MA, Chambrier I, Cook MJ, Marn MJ, Russell DA, Searcey M. Peptide directed phthalocyanine-gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers. RSC Med. Chem. 2021;12(2):288–292. DOI: 10.1039/D0MD00284D.
  34.  Kolesnikova TA, Gorin DA, Fernandes P, Kessel S, Khomutov GB, Fery A, Shchukin DG, Mohwald H. Nanocomposite microcontainers with high ultrasound sensitivity. Adv. Funct. Mater. 2010;20(7):1189–1195. DOI: 10.1002/adfm.200902233.
  35.  Novoselova MV, German SV, Abakumova TO, Perevoschikov SV, Sergeeva OV, Nesterchuk MV, Efimova OI, Petrov KS, Chernyshev VS, Zatsepin TS, Gorin DA. Multifunctional nanostructured drug delivery carriers for cancer therapy: Multimodal imaging and ultrasound-induced drug release. Colloids Surf B Biointerfaces. 2021;200:111576. DOI: 10.1016/j.colsurfb.2021.111576.
  36.  De Vry J, Martnez-Martnez P, Losen M, Temel Y, Steckler T, Steinbusch HW, De Baets MH, Prickaerts J. In vivo electroporation of the central nervous system: A non-viral approach for targeted gene delivery. Prog. Neurobiol. 2010;92(3):227–244. DOI: 10.1016/j.pneurobio.2010.10.001.
  37.  Zhang N, Li Z, Han X, Zhu Z, Li Z, Zhao Y, Liu Z, Lv Y. Irreversible electroporation: An emerging immunomodulatory therapy on solid tumors. Front. Immunol. 2022;12:811726. DOI: 10.3389/fimmu.2021.811726.
  38.  Massart R. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Transactions on Magnetics. 1981;17(2):1247–1248. DOI: 10.1109/TMAG.1981.1061188.
  39.  Gulyaev YV, Cherepenin VA, Taranov IV, Vdovin VA, Khomutov G B. Effect of ultrashort electric pulses on nanocomposite liposomes in aqueous medium. J. Commun. Technol. Electron. 2020;65:193–199. DOI: 10.1134/S1064226920020096.
  40.  Gulyaev YV, Cherepenin VA, Vdovin VA, Taranov IV, Yaroslavov AA, Kim VP, Khomutov GB. Pulsed electric field-induced remote decapsulation of nanocomposite liposomes with implanted conducting nanoparticles. J. Commun. Technol. Electron. 2015;60:1097–1108. DOI: 10.1134/ S1064226915100034.
  41.  Gulyaev YV, Cherepenin VA, Taranov IV, Vdovin VA, Khomutov GB. Activation of nanocomposite liposomal capsules in a conductive water medium by ultra-short electric exposure. J. Commun. Technol. Electron. 2021;66:88–95. DOI: 10.1134/S1064226921010022.
  42.  Landau LD, Lifshitz EM. Electrodynamics of Continuous Media. N.Y.: Elsevier; 2013. 475 p.
  43.  Schwan HP. Biophysics of the interaction of electromagnetic energy with cells and membranes. In: Grandolfo M, Michaelson SM, Rindi A, editors. Biological Effects and Dosimetry of Nonionizing Radiation. NATO Advanced Study Institutes Series. Vol. 49. Boston: Springer; 1983. P. 213–231. DOI: 10.1007/978-1-4684-4253-3_9.
  44.  Ovchinnikov YuA. Bioorganic Chemistry. M.: Prosveshcheniye; 1987. 815 p.
  45.  Kim VP, Ermakov AV, Glukhovskoy EG, Rakhnyanskaya AA, Gulyaev YuV, Cherepenin VA, Taranov IV, Kormakova PA, Potapenkov KV, Usmanov NN, Saletsky AM, Koksharov YuA, Khomutov GB. Planar nanosystems on the basis of complexes formed by amphiphilic polyamine, magnetite nanoparticles, and DNA molecules. Nanotechnol. Russia. 2014;9:280–287. DOI: 10.1134/ S1995078014030070.
  46.  Gulyaev YV, Cherepenin VA, Taranov IV, Vdovin VA, Yaroslavov AA, Kim VP, Khomutov GB. Remote decapsulation of nanocomposite liposomal capsules containing gold nanorods by ultrashort electric pulses. J. Commun. Technol. Electron. 2016;61:56–60. DOI: 10.1134/S1064226915120104.
  47.  Chede LS, Wagner BA, Buettner GR, Donovan MD. Electron spin resonance evaluation of buccal membrane fluidity alterations by sodium caprylate and L-menthol. Int. J. Mol. Sci. 2021;22(19):10708. DOI: 10.3390/ijms221910708.
Received: 
03.04.2025
Accepted: 
25.06.2025
Available online: 
03.07.2025
Published: 
30.09.2025