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

4 Citations (Scopus)

Abstract

While DNA and messenger RNA (mRNA) based therapies are currently changing the biomedical field, thedelivery of genetic materials remains the key problem preventing the wide introduction of thesemethods 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 reporton the design of a novel approach to format 50–150 nm calcium carbonate particles in the vaterite stateand 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 activelyinternalized by up to 99% of primary T-lymphocytes and exert minimal toxicity with the viability of490%. We demonstrate that these nanocarriers mediate more efficient transfection compared with thestandard electroporation method (90% vs. 51% for mRNA and 62% vs. 39% for plasmid DNA) in primaryhuman T-lymphocytes as a model of the hard to transfect type that is widely used in gene and celltherapy approaches. Importantly, these polymeric nanocarriers can be used in serum containing basicculture medium without special conditions and equipment, thus having potential for being introduced inclinical development. As a result, we have provided proof-of-principle that our nanosized containersrepresent 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

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