Multifunctional Plasmonic Core-Satellites Nanoprobe for Cancer Diagnosis and Therapy Based on a Cascade Reaction Induced by MicroRNA

Abstract

Constructing multifunctional plasmonic core-satellites (CS) nanoassembly for clinical cancer diagnosis and therapy has gained vast attention. Herein, we reported a doxorubicin (Dox)-loaded CS nanoprobe for microRNA (miRNA) detection, targeting drug release, and therapy evaluation. The plasmonic CS nanoprobe was constructed with uniformly distributional 50 nm (core) and 13 nm (satellites) gold nanoparticles (AuNPs), which were functionally assembled with a specific sequence of DNA and peptides. Anticancer drug Dox was loaded by intercalating into the GC-rich double strands. In the presence of target miRNA (miRNA-21 used as model), the constructed CS nanostructure was disassembled, producing characteristic localized surface plasmon resonance (LSPR) signals and releasing Dox. With the increase of the miRNA-21 concentration ranging from 0.01 to 1000 fM, a distinct blue shift of scattering spectra peak occurred, along with obvious color change from orange to green under a dark-field microscope (DFM), which can be used to detect miRNA at single-particle level. Meanwhile, it released Dox-induced apoptosis. Caspase-3 involved in apoptosis was then activated to cleave the specific peptide substrate, releasing fluorophore FAM from AuNPs. As a result, caspase-3 was detected based on restored fluorescence intensity, which was used to evaluate the therapy effectiveness. In a word, the multifunctional plasmonic CS nanoprobe can be used not only to image cellular miRNA-21 to distinguish tumor cells from normal cells, but also to release drugs and monitor the apoptotic process in situ by confocal imaging.

Carbon Dot-Encapsulated Plasmonic Core-Satellite Nanoprobes for Sensitive Detection of Cancer Biomarkers via Dual-Mode Colorimetric and Fluorometric Immunoassay

“…As shown in Figure S7, there are two characteristic peaks at 374.3 and 368.3 eV, which are the same as the binding energies of Ag 3d 3/2 and Ag 3d 5/2 of Ag(0). The splitting of the 3d doublet is deduced to be 6.0 eV, which agrees well with the theoretical value of Ag(0), 37 indicating that Ag exists in the metallic state. The Au 4f XPS spectrum consists of two prominent peaks at 83.9 and 87.7 eV, corresponding to the binding energies of Au 4f 7/2 and Au 4f 5/2 , respectively, indicating that HAuCl 4 was successfully reduced to metallic Au.…”

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

“…Also, doxorubicin was released, promoting apoptosis of the cancer cells and caspase-3 activation, which cleaved the peptides and increased the distance between the fluorophore and the nanoparticle, allowing fluorescence detection of the apoptotic process. 53 In summary, many different gold nanoconjugates have been designed and functionalized with moieties (Figure 3) targeting genes, proteins, or receptors specific to a certain cell type or tissue, enabling an increase in cell detection, targeting, and therapeutic efficacy. These nanoconjugates have been used to target different types of cancer, either as a monotherapy or in combination with other types of therapies, either given alone or also conjugated to nanoparticles, allowing the authors to target different mechanisms of action to increase the overall therapeutic effect obtained but also to overcome drug resistance.…”

Crosstalk Among circRNA/lncRNA, miRNA, and mRNA in Osteoarthritis

“… Chen et al (2018c) developed a computational model for disease association prediction to detect potential miRNA-disease associations accurately and efficiently. By studying three common human cancers ( Zhang et al, 2021b ), namely, colon cancer, esophagus cancer, and kidney cancer, many miRNAs were confirmed to be connected with the three kinds of cancer. In addition, many studies have proven that miRNA is related to the pathological processes of intervertebral disc degeneration ( Shi et al, 2021b ), muscle atrophy ( Zhang et al, 2021a ), and cardiovascular diseases ( Liu et al, 2021a ).…”