Phototheranostic Agents Based on Nonionic Heptamethine Cyanine for Realizing Synergistic Cancer Phototherapy.

Asymmetrical heptamethine cyanine with near-infrared (NIR) absorption is used for photothermal therapy (PTT) of cancer. Aiming to overcome the drawbacks caused by the high temperature of PTT, the development of asymmetrical heptamethine cyanine with photothermal and photodynamic properties is still an attractive strategy. Different from the traditional method of the heavy atom effect, in this work, the carboxyl or sulfonic groups are introduced into the indole ring or branch chain of asymmetrical heptamethine cyanine to afford a series of new phototherapy agents. After being encapsulated by DSPE-PEG2000 , BSS-Et NPs exhibit robust photostability, efficient reactive oxygen species generation (49%), and excellent photothermal conversion efficiency of about 37.6% under 808 nm laser irradiation. BSS-Et NPs possess passive tumor-targeting properties in vivo to not only visualize the tumor by NIR fluorescence imaging but also eliminate the tumor without any recurrence by photodynamic therapy and PTT synergistic therapy under laser irradiation. In addition, benefitting from the characteristics of organic small molecules, they can be metabolized quickly through the liver without inducing toxicity in the whole body. In general, this study provides a new direction for the development of multifunctional phototherapy agents for cancer treatment.

Multifaceted Elevation of ROS Generation for Effective Cancer Suppression.

The in situ lactate oxidase (LOx) catalysis is highly efficient in reducing oxygen to H2O2 due to the abundant lactate substrate in the hypoxia tumor microenvironment. Dynamic therapy, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and enzyme dynamic therapy (EDT), could generate reactive oxygen species (ROS) including ·OH and 1O2 through the disproportionate or cascade biocatalytic reaction of H2O2 in the tumor region. Here, we demonstrate a ROS-based tumor therapy by integrating LOx and the antiglycolytic drug Mito-LND into Fe3O4/g-C3N4 nanoparticles coated with CaCO3 (denoted as FGLMC). The LOx can catalyze endogenous lactate to produce H2O2, which decomposes cascades into ·OH and 1O2 through Fenton reaction-induced CDT and photo-triggered PDT. Meanwhile, the released Mito-LND contributes to metabolic therapy by cutting off the source of lactate and increasing ROS generation in mitochondria for further improvement in CDT and PDT. The results showed that the FGLMC nanoplatform can multifacetedly elevate ROS generation and cause fatal damage to cancer cells, leading to effective cancer suppression. This multidirectional ROS regulation strategy has therapeutic potential for different types of tumors.

A dicyanomethylene-4H-pyran-based fluorescence probe with high selectivity and sensitivity for detecting copper (II) and its bioimaging in living cells and tissue.

Copper (Cu) plays a significant role in the process of oxygenic photosynthesis in living systems. The detection of copper ion (Cu2+) is valuable and meaningful for further investigating the functions of Cu2+ under physiological and pathological conditions. In this paper, a novel fluorescence probe DCM-Cu based on the near-infrared (NIR) fluorophore dicyanomethylene-4H-pyran (DCM) was designed for Cu2+ detection. The probe DCM-Cu possessed characteristic of "turn-on" fluorescent signal in the presence of Cu2+ through the enhanced ICT process. It exhibited satisfactory sensitivity and selectivity toward Cu2+. A good linear correlation was observed between the concentrations of Cu2+ and the fluorescence intensities at 700 nm. The detection limit (LOD) of DCM-Cu toward Cu2+ was calculated to be 2.54 × 10-8 M. Importantly, DCM-Cu was successfully applied in the detection of Cu2+ in living MCF-7 cells and tumor tissue with low cytotoxicity. Therefore, this probe would have the potential to monitor cellular Cu2+ in the living system and be applied to the diagnosis of related diseases.

A novel DCM-based NIR fluorescent probe for detecting ozone and its bioimaging in live cells.

Nowadays, ozone has been widely applied in industry and medical therapies. However, excessive exposure to ozone can lead to lung dysfunction and many respiratory symptoms. As a member of reactive oxygen species (ROS), ozone was also involved in various physiology and pathology process. Given the fact of this, the effective detection of ozone in the atmosphere and biological system is of vital significance. Herein, we reported a novel dicyanomethylene-4H-pyran (DCM)-based fluorescent probe DCM-O3 with butenyl being the recognition moiety for monitoring ozone. The probe displayed high selectivity towards ozone, and its response towards ozone could be completed within 5 min under the optimal condition. Besides, a good linear correlation was obtained between the ozone concentrations (0-50 µM) and the corresponding fluorescent intensity at 560 nm, and the limit of detection (LOD) was calculated to be 6.2 × 10-7 M. Moreover, the probe DCM-O3 showed low cytotoxicity and was successfully applied to detect ozone in live cells. Given all the merits, the probe DCM-O3 could function as a robust tool for researchers to investigate ozone-related diseases in the complex biological environment.

The improved targeting of an aspirin prodrug albumin-based nanosystem for visualizing and inhibiting lung metastasis of breast cancer.

Lung metastasis is the principal reason for the majority of deaths from breast cancer. The nonsteroidal anti-inflammatory drug aspirin can prevent lung metastasis in breast tumors via inhibiting heparanase. However, the lack of specific targets and limited accumulation at the site of the tumor have thus far hindered the use of aspirin in oncotherapy. In this study, we developed the nanoplatform FA-BSA@DA and loaded it with the versatile aspirin prodrug DA to visualize and inhibit breast cancer metastasis via targeting heparanase. This nanosystem can be effectively targeted to folic acid (FA)-positive tumor cells, and would then subsequently release a high dose of DA, whose ester bond is specifically ruptured by H2O2 in the tumor microenvironment to afford the therapeutic drug aspirin and near-infrared (NIR) fluorescent reporter DCM. The released aspirin can effectively prevent breast cancer lung metastasis through the inhibition of heparanase activity, and the NIR fluorescent signals emitted from DCM can be used to monitor and evaluate the metastasis levels of breast cancer. Our results showed that the expression of heparanase was significantly decreased, and lung metastasis from breast cancer was effectively monitored and inhibited after treatment with FA-BSA@DA. Furthermore, the collaborative therapy nanoplatform FA-BSA@DA/DOX exhibited strong therapeutic effects in the treatment of breast cancer in vitro and in vivo via the introduction of doxorubicin (DOX) to the system, which resulted in an even stronger result due to its synergistic effects with aspirin. This heparanase-reliant strategy has profound significance for the extended development of nanoplatforms based on versatile aspirin prodrugs, which may offer a solution to clinically prevent breast cancer recurrence and lung metastasis.