Abstract
The design of nanoparticulate systems which can perform multiple synergistic functions in cells with high specificity and selectivity is of great importance in applications. Here we combine recent advances in DNA-gold nanoparticle self-assembly and sensing to develop gold nanoparticle dimers that are able to perform multiplexed synergistic functions within a cellular environment. These dimers can sense two mRNA targets and simultaneously or independently deliver one or two DNA-intercalating anticancer drugs (doxorubicin and mitoxantrone) in live cells. Our study focuses on the design of sophisticated nanoparticle assemblies with multiple and synergistic functions that have the potential to advance sensing and drug delivery in cells.
Highlights
P rogress in the field of nanoscience has rendered available a variety of inorganic nanoparticles in terms of their chemical composition and morphology and their properties
Owen et al designed a probe specific for the detection and isolation of viable CSC using flow cytometry via the specific detection of nanog mRNA, a marker that is highly expressed in cancer stem cells and that correlates with patient survival.[28]
The particles were functionalized with a shell of oligonucleotide sense strands, designed to capture a specific mRNA target
Summary
P rogress in the field of nanoscience has rendered available a variety of inorganic nanoparticles in terms of their chemical composition and morphology and their properties. Mirkin and co-workers synthesized AuNPs densely functionalized with a 3d monolayer of synthetic oligonucleotides termed spherical nucleic acids (SNAs).[8,16] It was demonstrated that SNAs are readily taken up by cells mainly via a caveole-mediated endocytosis pathway.[17−20] A striking observation of their study was that the oligonucleotides attached to the nanoparticle surface did not degrade by endocellular enzymes possibly due to the highly ionic and steric microenvironment around the nanoparticles, which prevented the function of DNase enzymes.[5,21] SNAs were further developed to include short, dye-functionalized oligonucleotide strands that could sense mRNA in cells in real time.[22−26] These particles were used to detect the survivin mRNA transcript. Sun and co-workers designed a hairpin nanoparticle probe targeting exon[8] of brca[1] mRNA, a human tumor suppressor gene that plays an important role in repairing damaged DNA, while Gu and co-workers focused on the detection of stat5b mRNA, which provides insight into tumor progression, in MCF 7 cells (human breast cancer).[24,25]
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