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A study of complexation and biological fate of polyethyleneimine-siRNA polyplexes in vitro and in vivo by fluorescence correlation spectroscopy and positron emission tomography imaging.
Ludtke, Tanja; Simó, Cristina; Gimenez Reyes, Santiago; Martinez Moro, Marta; Salvador, Cristian; Ritacco, Hernan; Andreozzi, Patrizia; Llop, Jordi; Moya, Sergio E.
Afiliación
  • Ludtke T; Soft Matter Nanotechnology, Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014, Donostia-San Sebastián, Spain. smoya@cicbiomagune.es.
  • Simó C; Soft Matter Nanotechnology, Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014, Donostia-San Sebastián, Spain. smoya@cicbiomagune.es.
  • Gimenez Reyes S; Radiochemistry and Nuclear Imaging laboratory, Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014, Donostia-San Sebastián, Spain. jllop@cicbiomagune.es.
  • Martinez Moro M; Soft Matter Nanotechnology, Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014, Donostia-San Sebastián, Spain. smoya@cicbiomagune.es.
  • Salvador C; Instituto de Fisica del Sur (IFISUR-CONICET), Av. Alem, Bahia Blanca, Argentina.
  • Ritacco H; Soft Matter Nanotechnology, Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014, Donostia-San Sebastián, Spain. smoya@cicbiomagune.es.
  • Andreozzi P; CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, Miramon Pasealekua, 196, Donostia-San Sebastián 20014, Spain.
  • Llop J; Instituto de Fisica del Sur (IFISUR-CONICET), Av. Alem, Bahia Blanca, Argentina.
  • Moya SE; Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, FI, Italy.
Nanoscale ; 16(7): 3525-3533, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38273800
ABSTRACT
A deeper knowledge on the formation and biological fate of polymer based gene vectors is needed for their translation into therapy. Here, polyplexes of polyethyleneimine (PEI) and silencing RNA (siRNA) are formed with theoretical N/P ratios of 2, 4 and 12. Fluorescence correlation spectroscopy (FCS) is used to study the formation of polyplexes from fluorescently labelled PEI and siRNA. FCS proves the presence of free PEI. From the analysis of the autocorrelation functions it was possible to determine the actual stoichiometry of polyplexes. FCS and fluorescence cross correlation spectroscopy (FCCS) are used to follow the fate of the polyplexes intracellularly. Polyplexes disassemble after 1 day inside cells. Positron emission tomography (PET) studies are conducted with radiolabelled polyplexes prepared with siRNA or PEI labelled with 2,3,5,6-tetrafluorophenyl 6-[18F]-fluoronicotinate ([18F]F-PyTFP). PET studies in healthy mice show that [18F]siRNA/PEI and siRNA/[18F]PEI polyplexes show similar biodistribution patterns with limited circulation in the bloodstream and accumulation in the liver. Higher activity for [18F]PEI in the kidney and bladder suggests the presence of free PEI.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietileneimina / ARN Bicatenario Límite: Animals Idioma: En Revista: Nanoscale Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietileneimina / ARN Bicatenario Límite: Animals Idioma: En Revista: Nanoscale Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido