Nitroreductase-Responsive Fluorescent "Off-On" Photosensitizer for Hypoxic Tumor Imaging and Dual-Modal Therapy.

Photothermal therapy synergized with photodynamic therapy for the treatment of tumors has emerged as a promising strategy. However, designing photosensitizers with both high photothermal efficiency and high photodynamic performance remains challenging. In contrast, the strategy of rationalizing the design of photosensitizers using the physiological properties of tumors to improve the photon utilization of photosensitizers during phototherapy is more advantageous than the approach of endowing a single photosensitizer with complex functions. Herein, we propose a molecular design (CyNP) to convert from photothermal therapy to photodynamic synergistic photothermal therapy based on the prevalent properties of hypoxic tumors. In the normoxic region of tumors, the deactivation pathway of CyNP excited state is mainly the conversion of photon energy to thermal energy; in the hypoxic region of tumors, CyNP is reduced to CyNH by nitroreductase, and the deactivation pathway mainly includes radiation leap, energy transfer between CyNP and oxygen, and conversion of photons energy to heat energy. This strategy enables real-time fluorescence detection of hypoxic tumors, and it also provides dual-mode treatment for photothermal and photodynamic therapy of tumors, achieving good therapeutic effects in vivo tumor treatment. Our study achieves more efficient tumor photoablation and provides a reference for the design ideas of smart photosensitizers.

Novel Lysosome-Targeting Fluorescence Off-On Photosensitizer for Near-Infrared Hypoxia Imaging and Photodynamic Therapy In Vitro and In Vivo.

Photodynamic therapy (PDT) has emerged as a new antitumor modality. Hypoxia, a vital characteristic of solid tumors, can be explored to stimulate the fluorescence response of photosensitizers (PSs). Considering the characteristics of PDT, the targeting of organelles employing PS would enhance antitumor effects. A new multifunctional cyanine-based PS (CLN) comprising morpholine and nitrobenzene groups was prepared and characterized. It generated fluorescence in the near-infrared (NIR) region in the presence of sodium dithionite (Na2S2O4) and nitroreductase (NTR). The response mechanism of CLN was well investigated, thus revealing that its obtained reduction product was CLNH. The obtained fluorescence and singlet oxygen quantum yield of CLNH were 8.65% and 1.60%, respectively. Additionally, the selective experiment for substrates indicated that CLN exhibited a selective response to NTR. Thus, CLN fluorescence could be selectively switched on and its fluorescence intensity increased, following a prolonged stay in hypoxic cells. Furthermore, fluorescence colocalization demonstrated that CLN could effectively target lysosomes. CLN could generate reactive oxygen species and kill tumor cells (IC50 for 4T1 cells was 7.4 µM under a hypoxic condition), following its response to NTR. NIR imaging and targeted PDT were finally applied in vivo.

a Versatile Schiff Base Chemosensor for the Determination of Trace Co2+, Ni2+, Cu2+, and Zn2+ in the Water and Its Bioimaging Applications.

In this work, a simple and versatile Schiff base chemosensor (L) was developed for the detection of four adjacent row 4 metal ions (Co2+, Ni2+, Cu2+, and Zn2+) through colorimetric or fluorescent analyses. L could recognize the target ions in solutions containing a wide range of other cations and anions. The recognition mechanisms were verified with a Job's plot, HR-MS assays, and 1H NMR titration experiments. Then, L was employed to develop colorimetric test strips and TLC plates for Co2+. Meanwhile, L was capable of quantitatively measuring the amount of target ions in tap water and river water samples. Notably, L was used for imaging Zn2+ in HepG2 cells, zebrafish, and tumor-bearing mice, which demonstrated its potential biological applications. Therefore, L can probably serve as a versatile tool for the detection of the target metal ions in environmental and biological applications.