Evaluating the tumor stratification with a lysosomal pH sensitive-probe by fluorescence lifetime imaging

Owing to the anaerobic metabolism in the tumor,abundant acidic metabolites are produced and accumulated in the cells.Therefore,the cells in different tumor layers are directly linked to the pH micro-environment.Nevertheless,due to the lack of robust tools,the high-efficient evaluation of the acidic micro-environment of tumor stratification faces the challenge of accurate diagnosis.We designed a new pH sensitive fluorescent lifetime probe target to lysosomes.As we expected,the fluorescence lifetime of PLN possesses a good linear fit to the pH value,which could detect the pH change at a single lysosome level in real time,and then evaluate the different acidity of tumor stratification.The probe PLN is successfully used to evaluate the tumor stratification by fluorescence lifetime imaging microscopy(FLIM)for the first time,which is of great significance in the preoperative diagnosis of clinical tumor treatment or evaluation of drug delivery effect.

Activatable photoacoustic bioprobe for visual detection of aging in vivo

Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including myocardial infarction, stroke, some age-related cancers, macular degeneration, osteoarthritis, neurodegeneration, and many others. In the body, the main manifestation of aging is cellular aging, which exists within tissues and has a local or global impact on tissue function. However, the lack of effective aging detection tools has always been an issue that cannot be ignored in the field of aging research. Therefore,it is necessary to construct a non-invasive tool for in vivo detection of aging. Here, we show that the photoacoustic probe(LGAL), which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to the hallmark of aging, and allows for the microscopic imaging of aging through the intact mice. Firstly, this tool LGAL has been successfully applied to detect senescence in cells, displaying stronger photoacoustic signals than normal cells. Then, by using the photoacoustic probe, the blood vessels and tissues inside the mice can be visualized. Young and elderly mice exhibit varying intensities of photoacoustic signals, marking the first time a probe has been used to explore the aging of blood vessels and tissues inside the mice. Finally, we monitored the changes in the degree of aging during tumor treatment under photoacoustic(PA) imaging for the first time. As the treatment time increased, the degree of aging of the tumor gradually deepened. We expect the powerful tool could be a noninvasive and powerful tool for the study of aging biology.

Cysteine-activated fluorescence/photoacoustic integrated probe for non-invasive diagnosis of drug-induced liver injury

Hepatotoxicity is a serious problem faced by clinical drugs,and long-term administration or overdose may lead to liver failure and even death of patients.Therefore,developing a reliable detection method for the early diagnosis and therapy of drug-induced liver injury(DILI)has significant meaning.Nearinfrared fluorescence(NIRF)and photoacoustic(PA)dual-modality tomography probes can be used for imaging with high sensitivity and high-resolution of disease-related markers in deep tissues.Here,we developed a novel Cys-activated NIRF and PA dual-modality imaging probe(CDR)for early diagnosis of DILI,for the first time.The organic molecular probe CDR could respond rapidly to Cys,resulting in the absorption peak red-shifted from 560 nm to 725 nm,which also leads to the activation of the PA725signal and NIRF765signal.In addition,the new probe CDR could be used for NIRF/PA imaging of exogenous and endogenous Cys level in live cells and mice.More importantly,CDR has also been successfully used for in situ detection of Cys in early DILI mice and evaluate the therapeutic effect of NAC.Therefore,the CDR might become a powerful tool to research the physiological effect of Cys and evaluate the degree of DILI.