A highly efficient and safe gene delivery platform based on polyelectrolyte core-shell nanoparticles for hard-to-transfect clinically relevant cell types

Yana Tarakanchikova (Corresponding Author), Albert Muslimov, Igor Sergeev, Kirill Lepik, Nikita Yolshin, Alexander Goncharenko, Kirill Vasilyev, Igor Eliseev, Anton Bukatin, Vladislav Sergeev, Sergey Pavlov, Alexey Popov, Igor Meglinski, Boris Afanasiev, Bogdan Parakhonskiy, Gleb Sukhorukov, Dmitry Gorin

Research output: Contribution to journalArticleScientificpeer-review

23 Citations (Scopus)

Abstract

While DNA and messenger RNA (mRNA) based therapies are currently changing the biomedical field, the delivery of genetic materials remains the key problem preventing the wide introduction of these methods into clinical practice. Therefore, the creation of new methods for intracellular gene delivery, particularly to hard-to-transfect, clinically relevant cell populations is a pressing issue. Here, we report on the design of a novel approach to format 50-150 nm calcium carbonate particles in the vaterite state and using them as a template for polymeric core-shell nanoparticles. We apply such core-shell nanoparticles as safe and efficient carriers for mRNA and pDNA. We prove that such nanocarriers are actively internalized by up to 99% of primary T-lymphocytes and exert minimal toxicity with the viability of >90%. We demonstrate that these nanocarriers mediate more efficient transfection compared with the standard electroporation method (90% vs. 51% for mRNA and 62% vs. 39% for plasmid DNA) in primary human T-lymphocytes as a model of the hard to transfect type that is widely used in gene and cell therapy approaches. Importantly, these polymeric nanocarriers can be used in serum containing basic culture medium without special conditions and equipment, thus having potential for being introduced in clinical development. As a result, we have provided proof-of-principle that our nanosized containers represent a promising universal non-viral platform for efficient and safe gene delivery.
Original languageEnglish
Pages (from-to)9576-9588
JournalJournal of Materials Chemistry B
Volume8
Issue number41
DOIs
Publication statusPublished - 7 Nov 2020
MoE publication typeA1 Journal article-refereed

Funding

Y. T. acknowledged the financial support from CIMO Fellowship (TM15-9729), EDUFI Fellowship (TM-17-10389) and Academy of Finland (project no. 326126). B. P. acknowledged the financial support from FWO (project FWOKAN2018002501). The work related to XRD and Raman Spectroscopy measurement financially supported by the Russian Ministry of Science and Higher Education (project No 0791-2020-006) (Y. T., A. B., I. E.). Part of this work related to the in vitro transcription of DNA/RNA was supported by the Russian Foundation for Basic Research (project no. 19-015-00098) (A. M.). The work related to in vitro cell experiments was supported by the Russian Foundation for Basic Research (project no. 19-29-04025) (K. L.). The work related to synthesis and material characterization was supported by the Russian Science Foundation between Russia and Belgium (FWO) [No. 20-45-01012] (G. S., A. M., Y. T.). Part of work related to the flow cytometry supported from the Russian Foundation for Basic Research (project no.18-29-08046) (D. G.).

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