Gene Silencing Using Multifunctionalized Gold Nanoparticles for Cancer Therapy.
Multifunctionalized gold nanobeacons (Au-nanobeacon) combine, in a single and unique platform, targeting, detection and silencing providing an effective impact in clinics boosting cancer theranostics. Here, we describe a nano-integrated platform based on Au-nanobeacons able to detect and inhibit gene expression specifically in cancer cells. The surfaces of gold nanoparticles (AuNPs) are functionalized with targeting peptides to enhance tumor cell recognition and uptake, and with fluorescently labeled antisense DNA hairpin oligonucleotides to detect AuNPs. These oligonucleotides, upon recognition and hybridization to the target, open their structure resulting in separating apart the dye and the quencher allowing the fluorophore to emit light and to monitor the intracellular interactions of AuNPs with the target and the specific silencing of gene expression. This strategy allows inhibiting KRAS gene expression in colorectal carcinoma cell lines with no relevant toxicity for healthy fibroblasts. Importantly, this nano-integrated platform can be easily adapted to hybridize with any specific target thus providing real benefits for the diagnosis and treatment of cancer.
UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus da Caparica, 2829-516, Caparica, Portugal.
Alexandra R
AR
Fernandes
UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus da Caparica, 2829-516, Caparica, Portugal. pmvb@fct.unl.pt.
Pedro V
PV
Baptista
D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D005434:Flow Cytometry; D020868:Gene Silencing; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D014408:Biomarkers, Tumor; D016376:Oligonucleotides, Antisense; D011092:Polyethylene Glycols; D006046:Gold; D016283:Proto-Oncogene Proteins p21(ras)
Au-nanobeacon; Colorectal carcinoma cell lines; Gene silencing; Gold nanoparticles; KRAS; Peptides; Targeted delivery