Document details
Delivery of Splice Switching Oligonucleotides by Amphiphilic Chitosan-Based Nanoparticles(Article)
Retrieving additional authors...
- aINEB-Instituto de Engenharia Biomédica, Universidade Do Porto (UPorto), Rua Alfredo Allen, 208, Porto, 4200-135, Portugal
- bi3S-Instituto de Investigação e Inovação em Saúde, UPorto, Porto, 4200-135, Portugal
- cCeNano2I, Department of Metallurgical and Materials Engineering, UFMG, Belo Horizonte, 31270-901, Brazil
- dFaculdade de Engenharia da UPorto (FEUP), Porto, 4200-319, Portugal
- eFaculdade de Medicina da UPorto (FMUP), Porto, 4200-319, Portugal
- fInstituto de Cieîncias Biomédicas Abel Salazar (ICBAS), UPorto, Porto, 4050-313, Portugal
Retrieving additional affiliations...
Abstract
Splice switching oligonucleotides (SSOs) are a class of single-stranded antisense oligonucleotides (ssONs) being used as gene therapeutics and demonstrating great therapeutic potential. The availability of biodegradable and biocompatible delivery vectors that could improve delivery efficiencies, reduce dosage, and, in parallel, reduce toxicity concerns could be advantageous for clinical translation. In this work we explored the use of quaternized amphiphilic chitosan-based vectors in nanocomplex formation and delivery of splice switching oligonucleotides (SSO) into cells, while providing insights regarding cellular uptake of such complexes. Results show that the chitosan amphiphilic character is important when dealing with SSOs, greatly improving colloidal stability under serum conditions, as analyzed by dynamic light scattering, and enhancing cellular association. Nanocomplexes were found to follow an endolysosomal route with a long lysosome residence time. Conjugation of a hydrophobic moiety, stearic acid, to quaternized chitosan was a necessary condition to achieve transfection, as an unmodified quaternary chitosan was completely ineffective. We thus demonstrate that amphiphilic quaternized chitosan is a biomaterial that holds promise and warrants further development as a platform for SSO delivery strategies. © 2015 American Chemical Society.
Indexed keywords
| EMTREE drug terms: | agaroseantisense oligonucleotidechitosan nanoparticleglucosamineluciferasen acetylglucosamineRNAsodium sulfatesplice switching oligonucleotidestearic acidunclassified drugantisense oligonucleotidechitosannanoparticle |
|---|---|
| EMTREE medical terms: | Articlecell activitycell populationcellular distributionchemical structurecomplex formationconcentration (parameters)concentration responseconjugationcontrolled studydispersiondrug delivery systemdrug releaseendosomefemalegenetic transfectionhumanhuman cellhydrophobicityin vitro studyincubation timeintracellular signalinglysosomemolecular stabilityparticle sizephoton correlation spectroscopypriority journalsurface propertyzeta potentialcell proliferationchemical phenomenachemistrydrug effectsgeneticsHeLa cell lineRNA splicing |
| MeSH: | Cell ProliferationChitosanDynamic Light ScatteringHeLa CellsHumansHydrophobic and Hydrophilic InteractionsNanoparticlesOligonucleotides, AntisenseRNA Splicing |
Chemicals and CAS Registry Numbers:
agarose, 9012-36-6; glucosamine, 3416-24-8, 4607-22-1; n acetylglucosamine, 7512-17-6; RNA, 63231-63-0; sodium sulfate, 7757-82-6; stearic acid, 57-11-4, 646-29-7; chitosan, 9012-76-4;
Chitosan; Oligonucleotides, Antisense
Funding details
| Funding sponsor | Funding number | Acronym |
|---|---|---|
| PIEF-GA-2011-300485 | ||
| Conselho Nacional de Desenvolvimento Científico e Tecnológico | ||
| Conselho Nacional de Desenvolvimento Científico e Tecnológico | ||
| Fundação para a Ciência e a Tecnologia See opportunities | HMSP-ICT/0020/2010,PTDC/CTM-NAN/NAN/115124/2009 | |
| Ministry of Science and Technology | SFRH/BPD/69110/2010,SFRH/BD/79930/2011 |
-
1
This work was cofinanced by Fundac?a?o para a Cie?ncia e a Tecnologia (FCT, Portugal) within projects HMSP-ICT/0020/2010 and PTDC/CTM-NAN/NAN/115124/2009. Additionally, P.M.D.M. acknowledges the support from the Marie Curie Actions of the European Community?s 7th Framework Program (PIEF-GA-2011-300485); J.C.S. acknowledges the graduate fellowship from Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq, Ministry of Science and Technology, Brazil); C.P.G. and V.L. acknowledge FCT for their scholarships (SFRH/BD/79930/2011 and SFRH/BPD/69110/2010). We thank M. L?zaro from the Bioimaging Center for Biomaterials and Regenerative Therapies (b.IMAGE) for help with confocal microscopy. 1H NMR and Cryo-SEM were performed at the Centro de Materiais da Universidade do Porto (CEMUP).
- ISSN: 15438384
- CODEN: MPOHB
- Source Type: Journal
- Original language: English
- DOI: 10.1021/acs.molpharmaceut.5b00538
- PubMed ID: 26702499
- Document Type: Article
- Publisher: American Chemical Society
Moreno, P.M.D.; INEB-Instituto de Engenharia Biomédica, Universidade Do Porto (UPorto), Rua Alfredo Allen, 208, Porto, Portugal;
© Copyright 2017 Elsevier B.V., All rights reserved.
Cited by 10 documents
Leiro, V.
, Parreira, P.
, Freitas, S.C.
(2018) Biomedical Applications of Functionalized Nanomaterials: Concepts, Development and Clinical Translation
(2018) Biomedical Applications of Functionalized Nanomaterials: Concepts, Development and Clinical Translation
Falzarano, M.S.
, Flesia, C.
, Cavalli, R.
(2018) Current Pharmaceutical Design
(2018) Current Pharmaceutical Design
Gomes, C.P.
, Lopes, C.D.F.
, Leitner, M.
(2017) Advanced Healthcare Materials
(2017) Advanced Healthcare Materials
View details of all 10 citations
{"topic":{"name":"Gene transfer; Polyethyleneimine; Polyethylenimine PEI","id":149,"uri":"Topic/149","prominencePercentile":99.691055,"prominencePercentileString":"99.691","overallScholarlyOutput":0},"dig":"0f2411b139bed5979f8f45f8a44b78ed096b81617a32070564d82ab8be035b74"}