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

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.

Recent Advances in the Preparation and Application of DNA-Encoded Metal Nanoclusters

“…The nature of protecting ligands is quite vital for synthesis of MNCs. Organic scaffolds, especially biomolecules, such as thiolates [34], polymers [35][36][37][38][39], proteins [40][41][42][43][44][45], and DNA [38,39], are widely used as protecting ligands in the chemical reduction processes [46][47][48]. Small-molecule thiolates, as one of the most commonly used protective agents, are capable of effectively controlling the size and shape of MNCs.…”

Recent advances in multifunctional dendrimer‐based complexes for cancer treatment

“…The multifunctional protein of immune system lactoferrin can be effective as a tumor-targeting ligand. Almowalad et al (2022) synthesized gold nanocages conjugated with a diaminobutyric PPI dendrimer and evaluated them with PC-3 prostate cancer cells. The data indicated a high transfection efficiency of the lactoferrin nanocomplex for plasmid DNA into prostate cancer cells.…”

Biomolecule-functionalized nanoformulations for prostate cancer theranostics

“…also showed enhanced gene transfection ability of Lactoferrin loaded with gold nanocages and conjugated with complexed DNA [178] . Recent advancement of the redox-responsive polyamine cationic dendrimersomes (dendrimer-based vesicles) was successfully validated against the PC treatment leading to possible drug-gene combination therapy, where such polyamine dendrimer (third generation) was modified with either bioactive molecule (camptothecin) or lipid (cholesterol or octadecyl chain) groups [179] , [180] , [181] , [182] . Another biopolymer chitosan nanoparticles were synthesized to deliver a fungal metabolite (TM2) from T. atroviride for anti-cancer activity against PC cells by activating caspase 3 and inhibiting BCL-2 expression in PC cells [183] .…”