MiR-206 conjugated gold nanoparticle based targeted therapy in breast cancer cells

Abstract

MicroRNAs (miRNAs) are single-stranded, non-coding, 19–25 nucleotide RNA molecules that have been observed to be dysregulated in many diseases including cancer. miRNAs have been known to play an important role in cellular proliferation, differentiation, migration, apoptosis, survival, and morphogenesis. Breast cancer is heterogeneous in nature and contributed extensively to the increased mortality rate. miRNA can either be tumor-suppressive or oncogenic in nature. The level of expression of miRNA changes according to the subtypes of cancer and the mutation responsible for different cancers. miRNA mimicry or inhibition are emerging possible therapies to maintain the level of miRNA inside the cells. In order to have proper miRNA mimicry, the major hurdle is to deliver the miRNA mimics at the site of tumor. Metallic nanoparticles with modified surface can be used to solve the problem of miRNA delivery. MiR-206 is reported to be down-regulated in Luminal-A type of breast cancer. In the current manuscript, we aim to modify the surface of gold-nanoparticles (AuNPs) with PEG moiety and allow miRNA to attach to it. The fabricated nano-complex, not only delivered miR-206 but also caused cell death in MCF-7 by arresting cells in the G0-G1 phase and inducing apoptosis by downregulating NOTCH 3.

Innovative approaches in transforming microRNAs into therapeutic tools

“…Furthermore, inorganic materials such as gold, graphene oxide, iron oxide and silica‐based materials are also capable of delivering miRNA. Chemically‐modified versions of gold particles with thiols, amino groups, and PEG have been utilized to deliver miRNA (Chaudhari et al, 2022; Fu et al, 2019). Modified anti‐miR‐155 with thiols was successfully delivered into a diabetic mouse model (Jia et al, 2017).…”

“…Modified anti‐miR‐155 with thiols was successfully delivered into a diabetic mouse model (Jia et al, 2017). Additionally, modification of the gold surface with PEG allows miR‐206 delivery to breast cancer cells (Chaudhari et al, 2022). Another study has shown the potential use of dextran‐coated iron oxide‐based nanoparticles to deliver miR‐29a to breast cancer cells (Yalcin, 2019).…”

Gold Nanoconjugates for miRNA Modulation in Cancer Therapy: From miRNA Silencing to miRNA Mimics

“…For instance, PEGylated gold nanoparticles were conjugated with a miR-206 mimic and tested on breast cancer cells in vitro , showing effective treatment by targeting the NOTCH 3 gene and arresting cells in the G0-G1 phase . In another study by Dang et al , the authors designed photoresponsive gold nanoshells conjugated to miR-34a to overcome the lack of specificity and efficacy observed in other studies.…”

“…For instance, PEGylated gold nanoparticles were conjugated with a miR-206 mimic and tested on breast cancer cells in vitro , showing effective treatment by targeting the NOTCH 3 gene and arresting cells in the G0-G1 phase. 27 In another study by Dang et al , the authors designed photoresponsive gold nanoshells conjugated to miR-34a to overcome the lack of specificity and efficacy observed in other studies. These nanocarriers released the miRNA upon stimulation with near-infrared light which led to a regulation of its downstream targets and decreased the function of triple negative breast cancer cells, namely their viability, proliferation, and motility.…”

The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy

“…Metal-based nanoparticles also can be used for miRNA delivery [ 145 ]. The gold nanoparticle is another attractive material for nucleic acid delivery.…”