Tuning the NIR photoabsorption of CuWO4-x nanodots with oxygen vacancies for CT imaging guided photothermal therapy of tumors.

A traditional CuWO4 semiconductor (Eg = 2.25 eV) shows photoabsorption in the visible range with an edge at ∼550 nm, limiting its application in near-infrared (NIR) laser-induced photothermal ablation therapy (PAT). To tune the NIR photoabsorption of CuWO4, we report a trisodium citrate-induced strategy for generating oxygen vacancies. CuWO4 and CuWO4-x nanoparticles are prepared by a facile coprecipitation-solvothermal method in the absence or presence of trisodium citrate (0.2-0.5 g) as the reducing agent. Without trisodium citrate, CuWO4 consists of aggregated particles, and its dispersion has a typical yellow-green color without NIR photoabsorption. With the addition of trisodium citrate from 0.2 to 0.5 g, CuWO4-x samples are composed of monodisperse nanodots with increased sizes from ∼2 to ∼6 nm, and the color of these dispersions becomes darker with increased NIR photoabsorption, that is, from 0.178 to 0.685 at 808 nm. As a result, the aqueous dispersion of CuWO4-x-0.5 nanodots prepared with 0.5 g trisodium citrate exhibits a high photothermal efficiency of 47.6% under 808 nm laser irradiation. Simultaneously, CuWO4-x-0.5 nanodots have high X-ray attenuation as a CT imaging agent due to the presence of a heavy metal element (W). When the CuWO4-x-0.5 dispersion is injected into the tumors of mice, the tumors can be observed by CT and thermal imaging. After 808 nm laser irradiation (1.0 W cm-2, 10 min), cancer cells in vivo can be efficiently ablated by the photothermal effects of CuWO4-x, without obvious toxicity and side effects. Therefore, CuWO4-x can act as a novel all-in-one agent for CT imaging-guided photothermal therapy of tumors.

Chitosan-mediated green synthesis and folic-acid modification of CuS quantum dots for photoacoustic imaging guided photothermal therapy of tumor.

CuS nanomaterials capped with artificial organic-molecules or polymers have been well demonstrated as efficient photothermal nanoagents for the therapy of tumor, but their biocompatibility and target ability should be improved. To address these problems, we have used chitosan (CS) as the biomacromolecule model and surface ligands to prepare CuS quantum dots (QDs) via a simple co-precipitation method. CuS-CS QDs are then conjugated with folic acid (FA). The resulting CuS-CS-FA QDs are composed of hexagonal phase nanodots with sizes of about 4 nm. FA modification process has no apparent influence on the size, phase and composition of the QDs. Furthermore, the zeta potential and infrared spectroscopy confirm the efficient conjugation of FA. CuS-CS-FA QDs exhibit strong near-infrared photoabsorption and high photothermal efficiency (47.0%). As a result of the presence of CS ligand and FA modification, CuS-CS-FA QDs have good biocompatibility and relatively high cellular uptake efficacy. When CuS-CS-FA QD dispersion is injected intravenously into the tumor-bearing mice, the photoacoustic imaging reveals that CuS-CS-FA QD can be efficiently targeted and accumulated in the tumor and reach the peak dose at 60 min. The irradiation of 1064-nm laser (1.0 W cm-2, 10 min) results in the efficient inhibition of tumor growth, without treatment-induced toxicity. Therefore, CuS-CS-FA QDs have great potential to become biocompatible multifunctional nanoagents for imaging guided therapy of tumor.

Synthesis of Bi2WO6-x nanodots with oxygen vacancies as an all-in-one nanoagent for simultaneous CT/IR imaging and photothermal/photodynamic therapy of tumors.

All-in-one nanoagents with a single-component and all-required functions have attracted increasing attention for the imaging-guided therapy of tumors, but the design and preparation of such nanoagents remain a challenge. Herein, we report the introduction of oxygen vacancies to traditional semiconductors with heavy-metal elements for tuning photoabsorption in the near infrared (NIR) region, by using Bi2WO6 (band-gap: ∼2.7 eV) as a model. Bi2WO6-x nanodots with sizes of ∼3 or ∼8 nm have been prepared by a facile coprecipitation-solvothermal method assisted by citric acid (CA, 0.1-1.5 g) as the reduction agent. CA confers the removal of O atoms from the [Bi2O2]2+ layer during the solvothermal process, resulting in the formation of plenty of oxygen vacancies in the Bi2WO6-x crystal. As a result, NIR photoabsorption of Bi2WO6-x nanodots can be remarkably enhanced with the increase of the CA amount from 0 to 1.0 g. Under irradiation of a single-wavelength (808 nm, 1.0 W cm-2) NIR laser, black Bi2WO6-x-CA1.0 nanodots can not only efficiently produce a sufficient amount of heat with a photothermal conversion efficiency of 45.1% for photothermal therapy, but also generate singlet oxygen (1O2) for photodynamic therapy. Furthermore, due to the presence of heavy-metal (Bi and W) elements, Bi2WO6-x-CA1.0 nanodots have high X-ray attenuation ability for CT imaging. After the Bi2WO6-x-CA1.0 nanodot dispersion is injected into the tumor-bearing mice, the tumor can be imaged by using CT and an IR thermal camera. After irradiation with a single-wavelength (808 nm, 1.0 W cm-2, 10 min) NIR laser, the tumor can be completely suppressed by the synergic photothermal and photodynamic effects of Bi2WO6-x-CA1.0 nanodots, without recurrence and treatment-induced toxicity. Therefore, Bi2WO6-x nanodots have great potential as a novel all-in-one nanoagent for the imaging and phototherapy of tumors.

In situ growth of Au nanoparticles on natural melanin as biocompatible and multifunctional nanoagent for efficient tumor theranostics.

Natural melanin has been demonstrated to be a biocompatible and efficient nanoagent for the photothermal ablation of tumors, but their practical applications are limited due to their lack of typical imaging functions (CT, MRI, etc.). Thus, to achieve multifunctional melanin-based nanoagents for imaging-guided therapy, for the first time, herein, we report the in situ growth of Au nanoparticles on natural melanin as a model through a simple and safe method. The as-synthesized samples are composed of melanin nanoparticles (diameter: ∼120 nm) whose surface are decorated by small Au nanoparticles with an adjustable size ranging from ∼10 to ∼40 nm. These Au-decorated melanin (Au-M) nanocomposites exhibit satisfactory near infrared (NIR) photoabsorption and high photothermal conversion efficiency of 42.3%. Furthermore, the Au-M nanocomposites have a high X-ray attenuation coefficient and exhibit excellent biocompatibility. When the Au-M solutions were injected into the tumor of a mouse, the tumor could be detected by X-ray computed tomography (CT), photoacoustic (PA) and thermal imaging, and then be thermally ablated under the illumination of an 808 nm laser. Therefore, these Au-M nanocomposites have great potential as a novel multifunctional and biocompatible nanoagent for imaging-guided photothermal tumor ablation.