Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects.

Photothermal agents (PTAs) with minimized side effects are critical for transforming cancer photothermal therapy (PTT) into clinical applications. However, most currently available PTAs lack true selective activation to reduce side effects because of heavy spectral overlap between photothermal agents and their corresponding products. This study reports the construction of activatable PTAs with target-initiated large spectral separation for highly effective reduction of side effects. Such designed probes involve two H2O2-activatable PTAs, aza-BOD-B1 (single activatable site) and aza-BOD-B2 (multiple activatable site). After interacting with H2O2, aza-BOD-B1 only displays a mild absorption redshift (60 nm) from 750 nm to 810 nm with serious spectral overlap, resulting in a mild photothermal effect on normal tissues upon 808 nm light irradiation. In contrast, aza-BOD-B2 displays a large absorption spectral separation (150 nm) from 660 nm to 810 nm, achieving true selective activation to minimize side effects during PTT of cancer. Besides, in vitro and in vivo investigations demonstrated that aza-BOD-B2 can specifically induce photothermal ablation of cancer cells and tumors while leaving normal sites undamaged, whereas aza-BOD-B1 exhibits undesirable side effects on normal cells. Our study provides a practical solution to the problem of undesired side effects of phototherapy, an advance in precision medicine.

A water-soluble fluorescent probe for real-time visualization of γ-glutamyl transpeptidase activity in living cells.

γ-glutamyl transpeptidase (GGT) is a kind of cell-surface enzyme that is overexpressed in many cancer cells. It is of great significance to develop an ideal tool for the diagnosis of GGT-rich cancer cells. Here, we reported a simple-structured but effective imaging probe for the detection of GGT activity. In the presence of GGT, the γ-glutamyl linkage could be cleaved specifically to produce amino-substituted product, resulting in significant fluorescence enhancement at 578 nm. Moreover, we successfully employed the probe to monitor GGT activity in HepG2 cells. We envisaged that such a simple but effective imaging tool could improve the practical applications for bioimaging.

An electron-deficiency-based framework for NIR-II fluorescence probes.

Fluorescent probes in the NIR-II region provide high bioimaging quality. Optimizing the probe structure to achieve NIR-II imaging is ongoing, but remains challenging. Herein, increasing the electron withdrawing ability of the substituent in monochlorinated BODIPY greatly adjusted the emission wavelength from the NIR-I to NIR-II region, giving an efficient design strategy of NIR-II probes.