TY - JOUR
T1 - A highly efficient and safe gene delivery platform based on polyelectrolyte core-shell nanoparticles for hard-to-transfect clinically relevant cell types
AU - Tarakanchikova, Yana
AU - Muslimov, Albert
AU - Sergeev, Igor
AU - Lepik, Kirill
AU - Yolshin, Nikita
AU - Goncharenko, Alexander
AU - Vasilyev, Kirill
AU - Eliseev, Igor
AU - Bukatin, Anton
AU - Sergeev, Vladislav
AU - Pavlov, Sergey
AU - Popov, Alexey
AU - Meglinski, Igor
AU - Afanasiev, Boris
AU - Parakhonskiy, Bogdan
AU - Sukhorukov, Gleb
AU - Gorin, Dmitry
N1 - Funding Information:
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.).
PY - 2020/11/7
Y1 - 2020/11/7
N2 - 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
490%. 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.
AB - 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
490%. 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.
UR - http://www.scopus.com/inward/record.url?scp=85094892993&partnerID=8YFLogxK
U2 - 10.1039/d0tb01359e
DO - 10.1039/d0tb01359e
M3 - Article
C2 - 33005912
AN - SCOPUS:85094892993
VL - 8
SP - 9576
EP - 9588
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
SN - 2050-7518
IS - 41
ER -