VirPorters: Insights into the action of cationic and histidine-rich cell-penetrating peptides

0549351 - ÚOCHB 2023 RIV GB eng J - Článek v odborném periodiku
Váňová, J. - Číhařová, B. - Hejtmánková, A. - Epperla, Chandra Prakash - Škvára, P. - Forstová, J. - Hubálek Kalbáčová, M. - Španielová, Hana
VirPorters: Insights into the action of cationic and histidine-rich cell-penetrating peptides.
International Journal of Pharmaceutics. Roč. 611, January (2022), č. článku 121308. ISSN 0378-5173. E-ISSN 1873-3476
Institucionální podpora: RVO:61388963
Klíčová slova: cell-penetrating peptide * endosomal escape * Galectin-3 assay * membrane damage * murine polyomavirus * pseudovirion
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.8, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1016/j.ijpharm.2021.121308

The utilization of nanoparticles for the intracellular delivery of theranostic agents faces one substantial limitation. Sequestration in intracellular vesicles prevents them from reaching the desired location in the cytoplasm or nucleus to deliver their cargo. We investigated whether three different cell-penetrating peptides (CPPs), namely, octa-arginine R8, polyhistidine KH27K and histidine-rich LAH4, could promote cytosolic and/or nuclear transfer of unique model nanoparticles—pseudovirions derived from murine polyomavirus. Two types of CPP-modified pseudovirions that carry the luciferase reporter gene were created: VirPorters-IN with CPPs genetically attached to the capsid interior and VirPorters-EX with CPPs noncovalently associated with the capsid exterior. We tested their transduction ability by luciferase assay and monitored their presence in subcellular fractions. Our results confirmed the overall effect of CPPs on the intracellular destination of the particles and suggested that KH27K has the potential to improve the cytosolic release of pseudovirions. None of the VirPorters caused endomembrane damage detectable by the Galectin-3 assay. Remarkably, a noncovalent modification was required to promote high transduction of the reporter gene and cytosolic delivery of pseudovirions mediated by LAH4. Together, CPPs in different arrangements have demonstrated their potential to improve pseudovirion invasion into cells, and these findings could be useful for the development of other nanoparticle-based delivery systems.
Trvalý link: http://hdl.handle.net/11104/0325362