A Non‐Invasive Nanoprobe for In Vivo Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque

Abstract

Vulnerable atherosclerotic (AS) plaque is the major cause of cardiovascular death. However, clinical methods cannot directly identify the vulnerable AS plaque at molecule level. Herein, osteopontin antibody (OPN Ab) and NIR fluorescence molecules of ICG co‐assembled Ti3C2 nanosheets are reported as an advanced nanoprobe (OPN Ab/Ti3C2/ICG) with enhanced photoacoustic (PA) performance for direct and non‐invasive in vivo visual imaging of vulnerable AS plaque. The designed OPN Ab/Ti3C2/ICG nanoprobes successfully realize obvious NIR fluorescence imaging toward foam cells as well as the vulnerable AS plaque slices. After intravenous injection of OPN Ab/Ti3C2/ICG nanoprobes into AS model mice, in vivo imaging results show a significantly enhanced PA signal in the aortic arch accumulated with vulnerable plaque, well indicating the remarkable feasibility of OPN Ab/Ti3C2/ICG nanoprobes to distinguish the vulnerable AS plaque. The proposed OPN Ab/Ti3C2/ICG nanoprobes not only overcome the clinical difficulty to differentiate vulnerable plaque, but also achieve the non‐invasively specific in vivo imaging of vulnerable AS plaque at molecule level, greatly promoting the innovation of cardiovascular diagnosis technology.

Ratiometric Semiconducting Polymer Nanoparticle for Reliable Photoacoustic Imaging of Pneumonia-Induced Vulnerable Atherosclerotic Plaque in Vivo

“…48,49 Fortunately, the PA 690 /PA 800 ratios of RSPN were independent of external interference (e.g., multiple interfering species, local concentration of probes, probe instability, physiological environments, etc.). Compared with traditional "single-signal output" PA probes, 28,30 RSPN possesses a unique internal reference and may provide accurate measurement of O 2…”

“…Compared with the fluorescent probes for atherosclerosis, − RSPN possessed the higher penetration depth, suitable for imaging of atherosclerosis induced vulnerable plaques in vivo. , Fortunately, the PA 690 /PA 800 ratios of RSPN were independent of external interference (e.g., multiple interfering species, local concentration of probes, probe instability, physiological environments, etc.). Compared with traditional “single-signal output” PA probes, , RSPN possesses a unique internal reference and may provide accurate measurement of O 2 •– level in complex physiological environments, through the self-calibration of PA 690 /PA 800 ratios.…”

“…Thus, it is highly desirable to develop noninvasive imaging techniques for visualizing O 2 •– within plaque, so as to assess the vulnerability of atherosclerosis in vivo. , At present, clinical detection methods for O 2 •– are based on the fluorescent imaging of dihydroethidium (DHE) in ex vivo tissue. , However, the insufficient penetration depth of fluorescence has limited its application in vivo. Interestingly, photoacoustic (PA) imaging has emerged as a promising novel biomedical imaging modality, with the characteristic of high resolution, deep tissue penetration and high contrast. − Although several photoacoustic probes have already been developed for imaging atherosclerotic plaque, − the accurate and dynamic assessment of O 2 •– level in atherosclerotic lesions are still limited by a variety of interference factors (e.g., local concentrations of probe, sophisticated microenvironment, etc. ). , …”

Nanotechnology for cardiovascular diseases

“… (G) OPN/Ti 3 C 2 /ICG nanoprobe for accurate PAI of vulnerable plaques. 83 OPN/Ti3C2/ICG possessed enhanced PA performance and high specificity to foam cells in vulnerable atherosclerotic plaques (copyright Wiley-VCH, 2020). …”

“… 144 Ge and his colleagues evaluated the feasibility of identifying vulnerable atherosclerotic plaques at the molecular level in vivo with noninvasive PAI nanoprobes. 83 They succeeded in fabricating osteopontin antibody (OPN Ab) and ICG (NIR fluorescence molecules) coassembled Ti 3 C 2 nanosheets (OPN Ab/Ti 3 C 2 /ICG), which possessed enhanced PA performance and high specificity for foam cells in vulnerable atherosclerotic plaques ( Figure 2 G). Moreover, targeted nanomaterial-based PA imaging usually coordinates with other imaging techniques, such as MRI, optical imaging, ultrasound, SPECT, and CT, to achieve more accurate detection of atherosclerotic plaques and thrombosis progression.…”