Lactoferrin- and dendrimer-bearing gold nanocages for stimulus-free DNA delivery to prostate cancer cells

Almowalad, Jamal and Laskar, Partha and Somani, Sukrut and Meewan, Jitkasem and Tate, Rothwelle J. and Dufès, Christine (2022) Lactoferrin- and dendrimer-bearing gold nanocages for stimulus-free DNA delivery to prostate cancer cells. International Journal of Nanomedicine, 17. pp. 1409-1421. ISSN 1176-9114 (https://doi.org/10.2147/IJN.S347574)

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Abstract

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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