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journal article·2024Open access

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

Tanja Ludtke, Cristina Simó, Santiago Gimenez Reyes, Marta Martinez Moro, Cristian Salvador, Hernan Ritacco, Patrizia Andreozzi, Jordi Llop, Sergio E. Moya

Nanoscale· Volume 16· Issue 7
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Source abstract

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.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

Polymers

OpenAlex topics: RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques · Silk-based biomaterials and applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

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

Instituto de Fisica del Sur (IFISUR-CONICET), Av. Alem, Bahia Blanca, Argentina

CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, Miramon Pasealekua, 196, Donostia-San Sebastián 20014, Spain

Department of Chemistry ‘Ugo Schiff’, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, FI, Italy

Funding

Ministerio de Ciencia e Innovación · Ministero dell’Istruzione, dell’Università e della Ricerca · Agencia Estatal de Investigación · Consejo Nacional de Investigaciones Científicas y Técnicas

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