Cargando…

Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia

Non-viral delivery of therapeutic nucleic acids (NA), including siRNA, has potential in the treatment of diseases with high unmet clinical needs such as acute myeloid leukaemia (AML). While cationic biomaterials are frequently used to complex the nucleic acids into nanoparticles, attenuation of char...

Descripción completa

Detalles Bibliográficos
Autores principales: Kont, Ayse, Mendonça, Monique C. P., Cronin, Michael F., Cahill, Mary R., O’Driscoll, Caitriona M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456197/
https://www.ncbi.nlm.nih.gov/pubmed/36077202
http://dx.doi.org/10.3390/ijms23179791
_version_ 1784785754128384000
author Kont, Ayse
Mendonça, Monique C. P.
Cronin, Michael F.
Cahill, Mary R.
O’Driscoll, Caitriona M.
author_facet Kont, Ayse
Mendonça, Monique C. P.
Cronin, Michael F.
Cahill, Mary R.
O’Driscoll, Caitriona M.
author_sort Kont, Ayse
collection PubMed
description Non-viral delivery of therapeutic nucleic acids (NA), including siRNA, has potential in the treatment of diseases with high unmet clinical needs such as acute myeloid leukaemia (AML). While cationic biomaterials are frequently used to complex the nucleic acids into nanoparticles, attenuation of charge density is desirable to decrease in vivo toxicity. Here, an anionic amphiphilic CD was synthesised and the structure was confirmed by Fourier-transform infrared spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and high-resolution mass spectrometry (HRMS). A cationic amphiphilic cyclodextrin (CD) was initially used to complex the siRNA and then co-formulated with the anionic amphiphilic CD. Characterisation of the co-formulated NPs indicated a significant reduction in charge from 34 ± 7 mV to 24 ± 6 mV (p < 0.05) and polydispersity index 0.46 ± 0.1 to 0.16 ± 0.04 (p < 0.05), compared to the cationic CD NPs. Size was similar, 161–164 nm, for both formulations. FACS and confocal microscopy, using AML cells (HL-60), indicated a similar level of cellular uptake (60% after 6 h) followed by endosomal escape. The nano co-formulation significantly reduced the charge while maintaining gene silencing (21%). Results indicate that blending of anionic and cationic amphiphilic CDs can produce bespoke NPs with optimised physicochemical properties and potential for enhanced in vivo performance in cancer treatment.
format Online
Article
Text
id pubmed-9456197
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94561972022-09-09 Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia Kont, Ayse Mendonça, Monique C. P. Cronin, Michael F. Cahill, Mary R. O’Driscoll, Caitriona M. Int J Mol Sci Article Non-viral delivery of therapeutic nucleic acids (NA), including siRNA, has potential in the treatment of diseases with high unmet clinical needs such as acute myeloid leukaemia (AML). While cationic biomaterials are frequently used to complex the nucleic acids into nanoparticles, attenuation of charge density is desirable to decrease in vivo toxicity. Here, an anionic amphiphilic CD was synthesised and the structure was confirmed by Fourier-transform infrared spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and high-resolution mass spectrometry (HRMS). A cationic amphiphilic cyclodextrin (CD) was initially used to complex the siRNA and then co-formulated with the anionic amphiphilic CD. Characterisation of the co-formulated NPs indicated a significant reduction in charge from 34 ± 7 mV to 24 ± 6 mV (p < 0.05) and polydispersity index 0.46 ± 0.1 to 0.16 ± 0.04 (p < 0.05), compared to the cationic CD NPs. Size was similar, 161–164 nm, for both formulations. FACS and confocal microscopy, using AML cells (HL-60), indicated a similar level of cellular uptake (60% after 6 h) followed by endosomal escape. The nano co-formulation significantly reduced the charge while maintaining gene silencing (21%). Results indicate that blending of anionic and cationic amphiphilic CDs can produce bespoke NPs with optimised physicochemical properties and potential for enhanced in vivo performance in cancer treatment. MDPI 2022-08-29 /pmc/articles/PMC9456197/ /pubmed/36077202 http://dx.doi.org/10.3390/ijms23179791 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kont, Ayse
Mendonça, Monique C. P.
Cronin, Michael F.
Cahill, Mary R.
O’Driscoll, Caitriona M.
Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia
title Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia
title_full Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia
title_fullStr Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia
title_full_unstemmed Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia
title_short Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia
title_sort co-formulation of amphiphilic cationic and anionic cyclodextrins forming nanoparticles for sirna delivery in the treatment of acute myeloid leukaemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456197/
https://www.ncbi.nlm.nih.gov/pubmed/36077202
http://dx.doi.org/10.3390/ijms23179791
work_keys_str_mv AT kontayse coformulationofamphiphiliccationicandanioniccyclodextrinsformingnanoparticlesforsirnadeliveryinthetreatmentofacutemyeloidleukaemia
AT mendoncamoniquecp coformulationofamphiphiliccationicandanioniccyclodextrinsformingnanoparticlesforsirnadeliveryinthetreatmentofacutemyeloidleukaemia
AT croninmichaelf coformulationofamphiphiliccationicandanioniccyclodextrinsformingnanoparticlesforsirnadeliveryinthetreatmentofacutemyeloidleukaemia
AT cahillmaryr coformulationofamphiphiliccationicandanioniccyclodextrinsformingnanoparticlesforsirnadeliveryinthetreatmentofacutemyeloidleukaemia
AT odriscollcaitrionam coformulationofamphiphiliccationicandanioniccyclodextrinsformingnanoparticlesforsirnadeliveryinthetreatmentofacutemyeloidleukaemia