Gold nanoparticles conjugated with DNA aptamer for photoacoustic detection of human matrix metalloproteinase-9

Abstract

Matrix metalloproteinase-9 (MMP-9) plays major roles in extracellular matrix (ECM) remodeling and membrane protein cleavage, suggesting a high correlation with cancer cell invasion and tumor metastasis. Here, we present a contrast agent based on a DNA aptamer that can selectively target human MMP-9 in the tumor microenvironment (TME) with high affinity and sensitivity. Surface modification of plasmonic gold nanospheres with the MMP-9 aptamer and its complementary sequences allows the nanospheres to aggregate in the presence of human MMP-9 through DNA displacement and hybridization. Aggregation of gold nanospheres enhances the optical absorption in the first near-infrared window (NIR-I) due to the plasmon coupling effect, thereby allowing us to detect the aggregated gold nanospheres within the TME via ultrasound-guided photoacoustic (US/PA) imaging. Selective and sensitive detection of human MMP-9 via US/PA imaging is demonstrated in solution of nanosensors with the pre-treatment of human MMP-9, in vitro in cell culture, and in vivo in a xenograft murine model of human breast cancer.

Photoacoustic detection of SARS-CoV-2 spike N501Y single-nucleotide polymorphism based on branched rolling circle amplification

“…Considering that the applicability of both AuNPs and RCA were fully demonstrated using simulated biological samples and real samples by other groups [ 21 , 53 , 54 ], we expect that the PA biosensor holds potential in analyzing complex samples. To investigate the influences of matrix effects, series dilutions of targets were prepared in buffer solution containing 5% FBS for BRCA and PA analysis.…”

Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications

“…Generally, nontargeted PA contrast agents refer to the imaging agents without any targeting unit, which are often used in biomedical research such as in vivo angiography, − biodistribution monitoring, − drug metabolism evaluation, ,, etc. In contrast, targeted PA contrast agents usually consist of a targeting unit such as aptamers, , antibodies, peptides, − and small-molecule ligands, − which connect with the additional PA generation components, enabling the specific readout of the biomarker or biological events in certain locations. Generally, to facilitate the targeted specificity, the biotargets are supposed to be overexpressed in disease sites or show low levels in off-target sites.…”

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

“…16g). 199 Specifically, this MMP-9 probe is based on two kinds of DNA-modified 15 nm-sized AuNSs. The first AuNSs (AuNS-1) features a surface which was modified with a double stranded aptamer for MMP-9 and its partial complementary sequence (comp-1).…”