TY  - JOUR
AB  - Nuclear pore complexes (NPCs) are sophisticated transporters assembled from diverse proteins termed nucleoporins (Nups). They control all nucleocytoplasmic transport and form a stringent barrier between the cytosol and the nucleus. While selective receptor‐mediated transport enables translocation of macromolecules up to striking sizes approaching megadalton‐scale, the upper cutoff for diffusion is at 40 kDa. Raising the cutoff is of particular importance for nuclear delivery of therapeutic nanoparticles, for example, gene and chemotherapy. In this work, we set out to present compounds capable of raising the cutoff to an extent enabling nuclear delivery of 6 kbp pDNA (150 kDa) in cultured human vascular endothelial cells. Of all tested compounds one is singled out, 1,6‐hexanediol (1,6‐HD). Our observations reveal that 1,6‐HD facilitates nuclear delivery of pDNA in up to 10–20% of the tested cells, compared to no delivery at all in control conditions. It acts by interfering with bonds between Nups that occupy the NPC channel and confer transport selectivity. It also largely maintains cell viability even at high concentrations. We envisage that 1,6‐HD may serve as a lead substance and usher in the design of potent new strategies to increase nuclear delivery of therapeutic nanoparticles.
AU  - Azzam, Ihab
AU  - Liashkovich, Ivan
AU  - Luchtefeld, Isabelle
AU  - Kouzel, Ivan U.
AU  - Shahin, Victor
DA  - 2019-06-13
DO  - 10.1002/btm2.10136
KW  - nanomedicine
KW  - nanoparticles
KW  - nuclear pores
KW  - pharmacology
KW  - physiology
LA  - eng
N1  - Bioengineering & Translational Medicine 4 (2019) 3, e10136, 1-6
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster)
N1  - The authors acknowledge the financial support by the Deutsche Forschungsgemeinschaft (SH 167/6‐1 and SH 167/9‐1)
PY  - 2019-06-13
TI  - Facilitating plasmid nuclear delivery by interfering with the selective nuclear pore barrier
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-78069470906
Y2  - 2024-11-23T22:15:59
ER  -