Histidine-Tagged Folate-Targeted Gold Nanoparticles for Enhanced Transgene Expression in Breast Cancer Cells In Vitro

Abstract

Nanotechnology has emerged as a promising treatment strategy in gene therapy, especially against diseases such as cancer. Gold nanoparticles (AuNPs) are regarded as favorable gene delivery vehicles due to their low toxicity, ease of synthesis and ability to be functionalized. This study aimed to prepare functionalized AuNPs (FAuNPs) and evaluate their folate-targeted and nontargeted pCMV-Luc-DNA delivery in breast cancer cells in vitro. CS was added to induce stability and positive charges to the AuNPs (Au-CS), histidine (Au-CS-His) to enhance endosomal escape and folic acid for folate-receptor targeting (Au-CS-FA-His). The FAuNP:pDNA nanocomplexes possessed favorable sizes (<135 nm) and zeta potentials (<−20 mV), strong compaction efficiency and were capable of pDNA protection against nuclease degradation. These nanocomplexes showed minimal cytotoxicity (>73% cell viability) and enhanced transgene activity. The influence of His was notable in the HER2 overexpressing SKBR3 cells, which produced higher gene expression. Furthermore, the FA-targeted nanocomplexes enhanced receptor-mediated endocytosis, especially in MCF-7 cells, as confirmed by the receptor competition assay. While the role of His may need further optimization, the results achieved suggest that these FAuNPs may be suitable gene delivery vehicles for breast cancer therapeutics.

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy

“…For instance, in a previous study, modification of gold nanoparticles with histidine, folate and chitosan resulted in the preparation of nanostructures with a size of 135 nm and less, which may pose a problem for their internalization in breast tumor cells. 305 The advances in biology have resulted in identification of novel receptors with overexpression in breast cancer. For instance, neuropilin-1 (NRP-1) shows upregulation in breast tumor cells.…”

“…However, it should be noted that different modifications of nanomaterials with polymers can increase their particle size. For instance, in a previous study, modification of gold nanoparticles with histidine, folate and chitosan resulted in the preparation of nanostructures with a size of 135 nm and less, which may pose a problem for their internalization in breast tumor cells 305 . The advances in biology have resulted in identification of novel receptors with overexpression in breast cancer.…”

Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells

“…The treatment of breast cancer is usually a multimodal approach that could possibly include surgery, radiation, chemotherapy and hormonal therapy [ 3 ]. Furthermore, the efficacy of the aforementioned therapeutic strategies is increasingly reduced; this is owed to the phenomenon of multidrug resistance (MDR) exhibited by various cancer types, and the incidence of dramatic adverse effects caused by the lack of selectivity of chemotherapeutic agents [ 4 , 5 ]. This situation necessitates further research into more efficient breast cancer preventive and treatment options with fewer adverse effects.…”

Next-generation engineered nanogold for multimodal cancer therapy and imaging: a clinical perspectives

“…Folic acid (FA), vitamin B9, is another tumor cell targeting agent that binds to folate receptors and facilitates intracellular uptake via endocytosis [ 130 ]. The folate receptors are absent in healthy non-proliferating cells while overexpressed in proliferating cancerous cells.…”