University of Oulu

Multilayered polyelectrolyte assemblies as delivery system for biomedical applications

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Author: Tarakanchikova, Yana1,2
Organizations: 1University of Oulu Graduate School
2University of Oulu, Faculty of Information Technology and Electrical Engineering, Electrical Engineering, Opto-Electronics and Measurement Technicues (OPEM)
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.9 MB)
Persistent link: http://urn.fi/urn:isbn:9789526231112
Language: English
Published: Oulu : University of Oulu, 2021
Publish Date: 2021-10-27
Thesis type: Doctoral Dissertation
Defence Note: Academic dissertation to be presented with the assent of the Doctoral Training Committee of Information Technology and Electrical Engineering of the University of Oulu for public defence in the OP auditorium (L10), Linnanmaa, on 3 November 2021, at 12 noon
Tutor: Professor Alexey Popov
Professor Igor Meglinski
Professor Seppo Vainio
Reviewer: Professor Andre Skirtach
Doctor Vladimir Sivakov
Opponent: Doctor Vladimir Sivakov
Doctor Anton Sadovoy
Description:

Abstract

Gene therapy is a rapidly developing medical field, which focuses on the utilization of therapeutic delivery of recombinant nucleic acids into a patient’s cells to treat or prevent a broad spectrum of diseases. However, several important obstacles remain before its wide introduction into clinical application can be implemented. One of the biggest bottlenecks is a lack of efficient and safe delivery technologies, particularly, for in vivo distribution. Additionally, standard requirements for carriers are still an open question (safety, minimal/absent toxicity and immunogenicity, sufficient packaging capacity, targeting, straight and low-cost large-scale Good Manufacturing Practice (GMP) production). Therefore, a growing variety of non-viral delivery platforms represent a promising alternative. Nanotechnology opens new possibilities for resolving biomedical issues. Polymer and hybrid micro- and core–shell nanoparticles are currently under development as a platform for safe and efficient gene delivery.

The present thesis describes the development of new safety gene delivery system based on polymer nanoparticles. The results show that nucleic acids (DNA/RNA) can be successfully imbedded into the nanoparticle structures and delivered to various types of cells. For the characterization of the biocompatibility of nanoparticles in vitro, two optical methods were considered. Compatibility with red blood cells (important for intravenous delivery) was assessed using optical tweezers. Capsule biodistribution in vivo was studied with fluorescence spectroscopy and a radiolabeling technique. The data and experience gained from this research open new prospects in the fields of delivery systems areas, gene therapy, and diagnostics in vivo and new possibilities for future clinical applications.

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Tiivistelmä

Geeniterapia on nopeasti kehittyvä lääketieteellinen ala, joka keskittyy rekombinanttisten nukleiinihappojen terapeuttisen annon hyödyntämiseen potilaan soluihin laajan kirjon tautien hoitamiseksi tai ehkäisemiseksi. On kuitenkin olemassa useita tärkeitä esteitä, ennen kuin sen laajaa käyttöönottoa kliinisessä sovelluksessa voidaan toteuttaa. Yksi suurimmista pullonkauloista on tehokkaiden ja turvallisten jakelutekniikoiden puute etenkin in vivo -jakelussa. Myös kiistanalainen vakiovaatimukset operaattoreille ovat edelleen avoin ongelma (turvallisuus, vähäinen / puuttuva myrkyllisyys ja immunogeenisuus, riittävä pakkauskapasiteetti, kohdennus, suora ja edullinen laajamittainen GMP-tuotanto). Siksi kasvava valikoima ei-viraalisia jakelualustoja on lupaava vaihtoehto. Nanoteknologia avaa uuden mahdollisuuden ratkaista biolääketieteelliset kysymykset. Polymeerisiä ja hybridimikro- ja ydin-kuori-nanohiukkasia kehitetään parhaillaan turvallisen ja tehokkaan geeninsiirron alustana.

Tässä opinnäytetyössä kuvataan polymeerisiin nanohiukkasiin perustuvan uuden turvallisuusgeenin kuljetusjärjestelmän kehittäminen. Tulokset osoittivat, että nukleiinihapot (DNA / RNA) voidaan upottaa onnistuneesti nanohiukkasten rakenteeseen ja toimittaa erityyppisiin soluihin. Nanohiukkasten biologisen yhteensopivuuden in vitro karakterisoimiseksi otettiin huomioon kaksi optista menetelmää. Yhteensopivuus punasolujen kanssa (tärkeä laskimoon annettaessa) arvioitiin optisilla pinseteillä. Kapselien biologinen jakautuminen in vivo mitattiin ja tutkittiin fluoresenssispektroskopialla ja radioleimaustekniikalla. Tästä tutkimuksesta saadut tiedot ja kokemukset avaavat uusia näkymiä jakelujärjestelmiin, geeniterapiaan ja diagnostiikkaan in vivo ja avaavat uusia mahdollisuuksia tulevassa kliinisessä sovelluksessa.

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Osajulkaisut / Original papers

Osajulkaisut eivät sisälly väitöskirjan elektroniseen versioon. / Original papers are not included in the electronic version of the dissertation.

  1. Tarakanchikova, Y., Stelmashchuk, O., Seryogina, E., Piavchenko, G., Zherebtsov, E., Dunaev, A., Popov, A., & Meglinski, I. (2018). Allocation of rhodamine-loaded nanocapsules from blood circulatory system to adjacent tissues assessed in vivo by fluorescence spectroscopy. Laser Physics Letters, 15(10), 105601. https://doi.org/10.1088/1612-202X/aad857

    Rinnakkaistallennettu versio / Self-archived version

  2. Tarakanchikova, Y., Seryogina, E., Piavchenko, G., Dunaev, A., Popov, A., Meglinsky, I., Stelmashchuk, O., & Zherebtsov, E. (2018). Noninvasive control of rhodamine-loaded capsules distribution in vivo. In V. V. Tuchin, D. E. Postnov, E. A. Genina, & V. L. Derbov (Eds.), Saratov Fall Meeting 2017: Optical Technologies in Biophysics and Medicine XIX (p. 179). SPIE. https://doi.org/10.1117/12.2315773

    Rinnakkaistallennettu versio / Self-archived version

  3. Avsievich, T., Tarakanchikova, Y., Zhu, R., Popov, A., Bykov, A., Skovorodkin, I., Vainio, S., & Meglinski, I. (2019). Impact of nanocapsules on red blood cells interplay jointly assessed by optical tweezers and microscopy. Micromachines, 11(1), 19. https://doi.org/10.3390/mi11010019

    Rinnakkaistallennettu versio / Self-archived version

  4. Avsievich, T., Tarakanchikova, Y. V., Popov, A., Karmenyan, A., Bykov, A., & Meglinski, I. (2019). Combined use of optical tweezers and scanning electron microscopy to reveal influence of nanoparticles on red blood cells interactions. In A. Amelink & S. K. Nadkarni (Eds.), Novel Biophotonics Techniques and Applications V (p. 14). SPIE. https://doi.org/10.1117/12.2526730

    Rinnakkaistallennettu versio / Self-archived version

  5. Tarakanchikova, Y., Alzubi, J., Pennucci, V., Follo, M., Kochergin, B., Muslimov, A., Skovorodkin, I., Vainio, S., Antipina, M. N., Atkin, V., Popov, A., Meglinski, I., Cathomen, T., Cornu, T. I., Gorin, D. A., Sukhorukov, G. B., & Nazarenko, I. (2020). Biodegradable nanocarriers resembling extracellular vesicles deliver genetic material with the highest efficiency to various cell types. Small, 16(3), 1904880. https://doi.org/10.1002/smll.201904880

    Rinnakkaistallennettu versio / Self-archived version

  6. Tarakanchikova, Y., Muslimov, A., Sergeev, I., Lepik, K., Yolshin, N., Goncharenko, A., Vasilyev, K., Eliseev, I., Bukatin, A., Sergeev, V., Pavlov, S., Popov, A., Meglinski, I., Afanasiev, B., Parakhonskiy, B., Sukhorukov, G., & Gorin, D. (2020). A highly efficient and safe gene delivery platform based on polyelectrolyte core–shell nanoparticles for hard-to-transfect clinically relevant cell types. Journal of Materials Chemistry B, 8(41), 9576–9588. https://doi.org/10.1039/D0TB01359E

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Series: Acta Universitatis Ouluensis. C, Technica
ISSN: 0355-3213
ISSN-E: 1796-2226
ISSN-L: 0355-3213
ISBN: 978-952-62-3111-2
ISBN Print: 978-952-62-3110-5
Issue: 809
Type of Publication: G5 Doctoral dissertation (articles)
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
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