The development of biocompatiable efficient photothermal coupling agent (PCA) for image-guided photothermal therapy of cancer has gained increasing interests in recent years. Although various PCAs have been developed, the clinical translations of these materials have been largely hindered by the potential biosafety issues and challenges of scaling-up manufactures. In this research, we proposed nano-sized indocyanine green (ICG) J-aggregate (IJA) as a promising PCA which is fabricated by a very facile method using clinical-approved ICG as the only excipient. The as-prepared IJA remains stable in various solution and shows a ~115 nm red-shift in absorption peak compared to free ICG. Importantly, IJA can be disassociated into free ICG again after internalized into cells and exhibits high biosafety comparable to ICG. The IJA performs well for photothermal therapy both in vitro and in vivo. In addition, the IJA can also be used as a good photoacoustic contrast agent and internalization-responsive fluorescence probe. The facile preparation, high safety and excellent theranostic performance indicated that IJA might be a promising one-component agent for cancer theranostics.

Inflammation is an immunological response involved in various inflammatory disorders ranging from neurodegenerative diseases to cancers. Luminol has been reported to detect myeloperoxidase (MPO) activity in an inflamed area through a light-emitting reaction. However, this method is limited by low tissue penetration and poor spatial resolution. Here, we fabricated a nanobubble (NB) doped with two tandem lipophilic dyes, red-shifting luminol-emitted blue light to near-infrared region through a process integrating bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). This BRET–FRET process caused a 24-fold increase in detectable luminescence emission over luminol alone in an inflammation model induced by lipopolysaccharide. In addition, the echogenicity of the BRET–FRET NBs also enables perfused tissue microvasculature to be delineated by contrast-enhanced ultrasound imaging with high spatial resolution. Compared with commercially available ultrasound contrast agent, the BRET–FRET NBs exhibited comparable contrast-enhancing capability but much smaller size and higher concentration. This bioluminescence/ultrasound dual-modal contrast agent was then successfully applied for imaging of an animal model of breast cancer. Furthermore, biosafety experiments revealed that multi-injection of luminol and NBs did not induce any observable abnormality. By integrating the advantages of bioluminescence imaging and ultrasound imaging, this BRET–FRET system may have the potential to address a critical need of inflammation imaging.

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The traditional method of labeling the nonpalpable breast cancer is placing a guidewire or metal marker guided by ultrasound or stereographic mammogram prior to surgery. However, the wire localization has a risk of displacement and could be an obstacle in the surgical course. To avoid these issues, we tried to combine the near-infrared (NIR) fluorescence dye dioctadecyltetramethyl indotricarbocyanine iodide (DiR) and microbubbles (MBs) to realize the dual-modality imaging for breast cancer microfoci intraoperative identification and guidance as a more efficient workflow. First, 24 mice were divided into three groups, injected with DiR nanoparticles (NPs), DiR MBs, and DiR MBs + ultrasound (US), and then, in vivo and ex vivo NIR fluorescence imaging was conducted. The distinction of fluorescence imaging intensity at the tumor site among the three groups was statistically significant (P < 0.001). Group 3 (DiR MBs + US) exhibited the highest fluorescence imaging intensity; the distinctions between group 3 and group 1 (DiR NPs) and group 3 and group 2 (DiR MBs) were both statistically significant (P = 0.001, P = 0.003), while the distinction between group 1 and group 2 was not statistically significant (P = 1.0). The results above validated the advantage of fluorescence imaging by using ultrasound-targeted MB destruction. Second, two kinds of subcutaneous breast cancer mice models [4T1-luc­(n = 5)/MCF-7­(n = 3)] received tumor resection, and NIR fluorescence and bioluminescence images were obtained to detect tumor residuals. We found that the small residual tumor tissues, metastatic lymph nodes, and even the surrounding infiltrated tissue all can be indicated by the fluorescence imaging and verified with bioluminescence and histological examination. In addition, the residual tumor cells appeared as tumor recurrence 22 days post operation and was confirmed with contrast-enhanced ultrasound (CEUS) in vivo. Thereby, ultrasound-targeted DiR MB destruction and then conversion into DiR NPs was feasible for intraoperative identification and guidance of nonpalpable breast cancer foci.

A UV vibrational Raman lidar has been built and used to make quantitative measurements of water vapor and aerosol optical properties over Xi'an, China. Vertical profiles of the water vapor mixing ratio and aerosol extinction coefficient are retrieved. The water vapor mixing ratio is calibrated with radiosonde data. The diurnal variations of the water vapor mixing ratio, aerosol extinction coefficient, and aerosol optical depth are obtained. The results obtained in the form of a time-height indicator (THI) display clearly showed the relationship between water vapor and aerosols, in which the gradual enhancement of water vapor density results in aerosol accumulation in the early morning, in particular in the lower troposphere. The seasonal variations of the water vapor mixing ratio and aerosol optical depth over Xi'an were observed and analyzed using the average monthly distribution obtained by lidar for the first time, which will provide useful scientific data and real-time monitoring methods for studying local climate change. #