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.

D-A Type NIR-II Organic Molecules: Strategies for the Enhancement Fluorescence Brightness and Applications in NIR-II Fluorescence Imaging-Navigated Photothermal Therapy.

NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasivity, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A-type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to their tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT-based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI-based single or multiimaging technologies are classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT.

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.