Thermosensitive drug-loading system based on copper sulfide nanoparticles for combined photothermal therapy and chemotherapy in vivo.

A phase-change material (PCM) is an efficient energy storage material, but its poor thermal conductivity has limited its application in nanomedicine research. In this study, we used the photothermal material copper sulfide (CuS) to tackle this challenge. The designed CuS-DOX-MBA@PCM nanoparticles (NPs) were prepared by a nanoprecipitation method, and were composed of CuS, the anticancer drug (DOX), and near-infrared (NIR) dyes (MBA) encapsulated with stearic acid and lauric acid, which are characterized by a low eutectic point close to human physiological temperature. Because the CuS-DOX-MBA@PCM NPs could release the drug quickly in physiological conditions, it implied that they could have potential as a promising drug-loading system. CuS-DOX-MBA@PCM NPs were utilized as an imaging-guided photothermal agent for photothermal therapy (PTT) combined with chemotherapy in cells and in a mice model. In vitro fluorescence imaging indicated the high uptake of CuS-DOX-MBA@PCM NPs in tumor cells due to enhanced permeability and retention effects, while in vivo experiments showed that the tumor growth in tumor-bearing mice models could be inhibited by the CuS-DOX-MBA@PCM NPs. Such an evident enhanced tumor inhibition could be attributed to the synergistic effect of the DOX chemotherapy and the photothermal therapy with a safe laser irradiation at 808 nm with a power density of 1.0 W cm-2. Furthermore, this combined therapy offers the possibility to lower the dosage of DOX in anticancer therapy, which would thus decrease the toxic effects on cancer patients. The results from this study confirmed the effect of CuS-DOX-MBA@PCM NPs for use as a chemo-photothermal therapy and the clinical value of the designed thermosensitive drug-loading system in the field of combined cancer therapy.

GSH-Activated Light-Up Near-Infrared Fluorescent Probe with High Affinity to αvß3 Integrin for Precise Early Tumor Identification.

The development of tumor-associated, stimuli-driven, turn-on near-infrared (NIR) fluorophores requires urgent attention because of their potential in selective and precise tumor diagnosis. Herein, we describe a NIR fluorescent probe (CyA-cRGD) comprised of a fluorescence reporting unit (a cyanine dye) linked with a GSH-responsive unit (nitroazo aryl ether group) and a tumor-targeting unit (cRGD). The NIR fluorescence of CyA-cRGD with sensitive and selective response to GSH can act as a direct off-on signal reporter for GSH monitoring. Notably, CyA-cRGD possesses improved biocompatibility compared with CyA, which is highly desirable for in vivo fluorescence tracking of cancer. Confocal fluorescence imaging confirmed the tumor-targeting capability and GSH detection ability of CyA-cRGD in tumor cells, normal cells, and coincubated tumor /normal cells and in the three-dimensional multicellular tumor spheroid. Furthermore, it was validated that CyA-cRGD could detect tumor precisely in GSH and integrin αvß 3 high-expressed tumor-bearing mouse models. Importantly, it was confirmed that CyA-cRGD possessed high efficiency for early-stage tumor imaging in mouse models with tumor cells implanted within 72 h. This method provided significant advances toward more in-depth understanding and exploration of tumor imaging, which may potentially be applied for clinical early tumor diagnosis.