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Evaluation of amino-functional polyester dendrimers based on Bis-MPA as nonviral vectors for siRNA delivery
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
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2018 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, no 8, article id 2028Article in journal (Refereed) Published
Abstract [en]

Herein, we present the first evaluation of cationic dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) as nonviral vectors for transfection of short interfering RNA (siRNA) in cell cultures. The study encompassed dendrimers of generation one to four (G1-G4), modified to bear 6-48 amino end-groups, where the G2-G4 proved to be capable of siRNA complexation and protection against RNase-mediated degradation. The dendrimers were nontoxic to astrocytes, glioma (C6), and glioblastoma (U87), while G3 and G4 exhibited concentration dependent toxicity towards primary neurons. The G2 showed no toxicity to primary neurons at any of the tested concentrations. Fluorescence microscopy experiments suggested that the dendrimers are highly efficient at endo-lysosomal escape since fluorescently labeled dendrimers were localized specifically in mitochondria, and diffuse cytosolic distribution of fluorescent siRNA complexed by dendrimers was observed. This is a desired feature for intracellular drug delivery, since the endocytic pathway otherwise transfers the drugs into lysosomes where they can be degraded without reaching their intended target. siRNA-transfection was successful in C6 and U87 cell lines using the G3 and G4 dendrimers followed by a decrease of approximately 20% of target protein p42-MAPK expression.

Place, publisher, year, edition, pages
MDPI AG , 2018. Vol. 23, no 8, article id 2028
Keywords [en]
Bis-MPA, Dendrimer, Monodisperse, Polycation, RNAi, SiRNA
National Category
Polymer Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-238030DOI: 10.3390/molecules23082028ISI: 000445295500193Scopus ID: 2-s2.0-85053600476OAI: oai:DiVA.org:kth-238030DiVA, id: diva2:1278866
Note

Export Date: 30 October 2018; Article; CODEN: MOLEF; Correspondence Address: Malkoch, M.; Fiber and Polymer Technology, KTH Royal Institute of TechnologySweden; email: malkoch@kth.se

QC 20190115

Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved

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Stenström, PatrikZhang, YuningMalkoch, Michael

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