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Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells

BACKGROUND: The use of gene therapy to treat prostate cancer is hampered by the lack of effective nanocarriers that can selectively deliver therapeutic genes to cancer cells. To overcome this, we hypothesize that conjugating lactoferrin, a tumor-targeting ligand, and the diaminobutyric polypropyleni...

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Autores principales: Almowalad, Jamal, Laskar, Partha, Somani, Sukrut, Meewan, Jitkasem, Tate, Rothwelle J, Dufès, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968073/
https://www.ncbi.nlm.nih.gov/pubmed/35369035
http://dx.doi.org/10.2147/IJN.S347574
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author Almowalad, Jamal
Laskar, Partha
Somani, Sukrut
Meewan, Jitkasem
Tate, Rothwelle J
Dufès, Christine
author_facet Almowalad, Jamal
Laskar, Partha
Somani, Sukrut
Meewan, Jitkasem
Tate, Rothwelle J
Dufès, Christine
author_sort Almowalad, Jamal
collection PubMed
description BACKGROUND: The use of gene therapy to treat prostate cancer is hampered by the lack of effective nanocarriers that can selectively deliver therapeutic genes to cancer cells. To overcome this, we hypothesize that conjugating lactoferrin, a tumor-targeting ligand, and the diaminobutyric polypropylenimine dendrimer into gold nanocages, followed by complexation with a plasmid DNA, would enhance gene expression and anti-proliferation activity in prostate cancer cells without the use of external stimuli. METHODS: Novel gold nanocages bearing lactoferrin and conjugated to diaminobutyric polypropylenimine dendrimer (AuNCs-DAB-Lf) were synthesized and characterized. Following complexation with a plasmid DNA, their gene expression, cellular uptake and anti-proliferative efficacies were evaluated on PC-3 prostate cancer cells. RESULTS: AuNCs-DAB-Lf was able to complex DNA at conjugate: DNA weight ratios 5:1 onwards. Gene expression was at its highest after treatment with AuNCs-DAB-Lf at a weight ratio of 10:1, as a result of a significant increase in DNA uptake mediated by the conjugate at that ratio in PC-3 cells. Consequently, the anti-proliferative activity of AuNCs-DAB-Lf-DNA encoding TNFα was significantly improved by up to 9-fold compared with DAB dendriplex encoding TNFα. CONCLUSION: Lactoferrin-bearing dendrimer-conjugated gold nanocages are highly promising gene delivery systems for the treatment of prostate cancer.
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spelling pubmed-89680732022-04-01 Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells Almowalad, Jamal Laskar, Partha Somani, Sukrut Meewan, Jitkasem Tate, Rothwelle J Dufès, Christine Int J Nanomedicine Original Research BACKGROUND: The use of gene therapy to treat prostate cancer is hampered by the lack of effective nanocarriers that can selectively deliver therapeutic genes to cancer cells. To overcome this, we hypothesize that conjugating lactoferrin, a tumor-targeting ligand, and the diaminobutyric polypropylenimine dendrimer into gold nanocages, followed by complexation with a plasmid DNA, would enhance gene expression and anti-proliferation activity in prostate cancer cells without the use of external stimuli. METHODS: Novel gold nanocages bearing lactoferrin and conjugated to diaminobutyric polypropylenimine dendrimer (AuNCs-DAB-Lf) were synthesized and characterized. Following complexation with a plasmid DNA, their gene expression, cellular uptake and anti-proliferative efficacies were evaluated on PC-3 prostate cancer cells. RESULTS: AuNCs-DAB-Lf was able to complex DNA at conjugate: DNA weight ratios 5:1 onwards. Gene expression was at its highest after treatment with AuNCs-DAB-Lf at a weight ratio of 10:1, as a result of a significant increase in DNA uptake mediated by the conjugate at that ratio in PC-3 cells. Consequently, the anti-proliferative activity of AuNCs-DAB-Lf-DNA encoding TNFα was significantly improved by up to 9-fold compared with DAB dendriplex encoding TNFα. CONCLUSION: Lactoferrin-bearing dendrimer-conjugated gold nanocages are highly promising gene delivery systems for the treatment of prostate cancer. Dove 2022-03-25 /pmc/articles/PMC8968073/ /pubmed/35369035 http://dx.doi.org/10.2147/IJN.S347574 Text en © 2022 Almowalad et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Almowalad, Jamal
Laskar, Partha
Somani, Sukrut
Meewan, Jitkasem
Tate, Rothwelle J
Dufès, Christine
Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells
title Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells
title_full Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells
title_fullStr Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells
title_full_unstemmed Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells
title_short Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells
title_sort lactoferrin- and dendrimer-bearing gold nanocages for stimulus-free dna delivery to prostate cancer cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968073/
https://www.ncbi.nlm.nih.gov/pubmed/35369035
http://dx.doi.org/10.2147/IJN.S347574
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