Authors: Jinhwan Kim, Anthony M Yu, Kelsey P. Kubelick, Stanislav Y. Emelianov
Fig. 5. Spectroscopic analysis and PAT of the MMP sensor in an in vivo mouse model of breast cancer. (a) PA intensity from 680 nm to 970 nm of the MMP sensor in the tumor region and assorted controls – saline only and control sensor. Black dashed line marks 710 nm. (b) Overlaid photoacoustic tomography of saline, control sensor, and MMP sensor-injected mice. The volumes of skin and surface vasculature (532 nm) are colored in yellow and aggregated nanoparticles (710 nm) are colored in red, with the light blue dashed line indicating the tumor boundary. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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 microenvi-ronment (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.
Citation
J. Kim, A. M. Yu, K. P. Kubelick, and S. Y. Emelianov, “Gold nanoparticles conjugated with DNA aptamer for photoacoustic detection of human matrix metalloproteinase-9,” Photoacoustics, vol. 25, p. 100307, 2022/03/01/ 2022, doi: https://doi.org/10.1016/j.pacs.2021.100307.
