Aggregation-Induced Emission Luminogens Married to 2D Black Phosphorus Nanosheets for Highly Efficient Multimodal Theranostics.

Inspired by the respective advantages of aggregation-induced emission (AIE)-active photosensitizers and black phosphorus nanomaterials in cancer treatment, the facile construction of novel AIE photosensitizers married to 2D black phosphorus nanosheets and their application for multimodal theranostics are demonstrated. The developed nanomaterial simultaneously possesses distinctive properties and multiple functions including excellent stability, good biocompatibility, intensive fluorescence emission in the NIR region, high-performance reactive oxygen species generation, good photothermal conversion efficiency, outstanding cellular uptake, and effective accumulation at the tumor site. Both in vitro and in vivo evaluation show that the presented nanotheranostic system is an excellent candidate for NIR fluorescence-photothermal dual imaging-guided synergistic photodynamic-photothermal therapies. This study thus not only extends the applications scope of AIE and black phosphorus materials, but also offers useful insights into designing a new generation of cancer theranostic protocol for potential clinical applications.

A multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor cells.

We report the design and fabrication of a multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor. The integration of the dual-stimulus of an acidic microenvironment and laser irradiation with the triple-synergistic therapy of doxorubicin, photothermal and siRNA offers excellent therapeutic performance for drug resistant tumor cells with high specificity and little side effects.

DNA-assisted upconversion nanoplatform for imaging-guided synergistic therapy and laser-switchable drug detoxification.

The side effects of chemotherapy bring significant physical and psychological suffering to patients. To solve this urgent medical problem, Yb3+ and Er3+ co-doped NaLuF4 upconversion nanoparticles (UCNPs) were constructed for upconversion luminescence (UCL)-labeled diagnosis under 980 nm laser irradiation. The UCNPs were then modified layer by layer with polypyrrole and a special programming DNA segment as photothermal conversion agents and controllable drug carriers, respectively. The nanoplatform was successfully used for imaging-guided synergistic therapy (photothermal therapy and chemotherapy) at a safe power density (300 mW cm-2), and DNA-assisted detoxification at lower temperature in cancer cells when the laser off. The synergistic therapy of the nanoplatform achieved a higher therapeutic index (∼85%) than chemotherapy only (∼44%) and photothermal therapy only (∼25%) in vitro. In vivo experiments also suggested that the nanoplatform had a higher therapeutic effect and lower side effects. The toxicity study was also evaluated, indicating the nanoplatform is low toxic to living system. This multifunctional upconversion nanoplatform provided an innovative method for imaging-guided photothermal-chemotherapy and laser-switchable drug detoxification.

Covalent bridging of surface functionalized Fe3O4 and YPO4:Eu nanostructures for simultaneous imaging and therapy.

Magnetic luminescent hybrid nanostructures (MLHN) have received a great deal of attention due to their potential biomedical applications such as thermal therapy, magnetic resonance imaging, drug delivery and intracellular imaging. We report the development of bifunctional Fe3O4 decorated YPO4:Eu hybrid nanostructures by covalent bridging of carboxyl PEGylated Fe3O4 and amine functionalized YPO4:Eu particles. The surface functionalization of individual nanoparticulates as well as their successful conjugation was evident from Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta-potential and transmission electron microscopy (TEM) studies. X-ray diffraction (XRD) analysis reveals the formation of highly crystalline hybrid nanostructures. TEM micrographs clearly show the binding/anchoring of 10 nm Fe3O4 nanoparticles onto the surface of 100-150 nm rice grain shaped YPO4:Eu nanostructures. These MLHN show good colloidal stability, magnetic field responsivity and self-heating capacity under an external AC magnetic field. The induction heating studies confirmed localized heating of MLHN under an AC magnetic field with a high specific absorption rate. Photoluminescence spectroscopy and fluorescence microscopy results show optical imaging capability of MLHN. Furthermore, successful internalization of these MLHN in the cells and their cellular imaging ability are confirmed from confocal microscopy imaging. Specifically, the hybrid nanostructure provides an excellent platform to integrate luminescent and magnetic materials into one single entity that can be used as a potential tool for hyperthermia treatment of cancer and cellular imaging.

Unexpected high photothemal conversion efficiency of gold nanospheres upon grafting with two-photon luminescent ruthenium(II) complexes: A way towards cancer therapy?

The design and development of functional hybrid nanomaterials is currently a topic of great interest in biomedicine. Herein we investigated the grafting of Ru(II) polypyridyl complexes onto gold nanospheres (Ru@AuNPs) to improve the particles' near infrared (NIR) absorption, and ultimately allow for application in photothermal cancer therapy. As demonstrated in this article, these ruthenium(II) complexes could indeed significantly enhance gold nanospheres' two-photon luminescence (PTL) intensity and photothermal therapy (PTT) efficiency. The best dual functional nanoparticles of this study were successfully used for real-time luminescent imaging-guided PTT in live cancer cells. Furthermore, in vivo tumor ablation was achieved with excellent treatment efficacy under a diode laser (808 nm) irradiation at the power density of 0.8 W/cm(2) for 5 min. This study demonstrates that the coupling of inert Ru(II) polypyridyl complexes to gold nanospheres allows for the enhancement of two-photon luminescence and for efficient photothermal effect.

An imaging-guided platform for synergistic photodynamic/photothermal/chemo-therapy with pH/temperature-responsive drug release.

To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating photosensitive Au25(SR)18 - (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug (doxorubicin, DOX) onto the surface of mesoporous silica coated core-shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light.

Photoluminescent biocompatible silicon nanoparticles for cancer theranostic applications.

Silicon nanoparticles (SiNPs) obtained by mechanical grinding of porous silicon have been used for visualization of living cells in vitro. It was found that SiNPs could penetrate into the cells without any cytotoxic effect up to the concentration of 100 µg/ml. The cell cytoplasm was observed to be filled by SiNPs, which exhibited bright photoluminescence at 1.6 eV. SiNPs could also act as photosensitizers of the singlet oxygen generation, which could be used in the photodynamic therapy of cancer. These properties of SiNPs are discussed in view of possible applications in theranostics (both in therapy and in diagnostics).

Monitoring of bactericidal action of laser by in vivo imaging of bioluminescent E. coli in a cutaneous wound infection.

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. This study aimed to evaluate the bactericidal action of an 810-nm diode laser in a cutaneous wound infection. An Escherichia coli strain was transformed with a shuttle vector (pRB474) containing firefly luciferase gene from Photinus pyralis resulting in a bioluminescent phenotype. Because firefly luciferase is an enzyme and as such is prone to inactivation at elevated temperature, the first phase has consisted in evaluating in vitro the effect of temperature elevation (30, 40, 50, and 60 degrees C for 2 min) on bacteria bioluminescence. The second phase was performed in vivo. Two full-thickness circular, 14-mm diameter wounds (control and laser-irradiated) were induced on rats. Wound infection was carried out using a suspension (50 microl PBS) containing 5 x 10(7) cells of bioluminescent E. coli (10(9) cells/ml). Thirty minutes later, light irradiation was performed with an 810-nm diode laser (P = 10 W, psi = 1.4 cm, fluence: 130, 195, and 260 J/cm2). Temperature was measured within each wound with a noncontact infrared thermometer. Light emission of the bioluminescent bacteria was monitored in vivo by a bioluminescence imaging system before and at 4, 8, 24, and 48 h after laser irradiation. In vitro, bacteria bioluminescence is not affected when temperature is maintained at 50 degrees C for 2 min. In vivo, bioluminescence imaging showed that at 4 h, the viability of E. coli was reduced when compared to the control (CTRL) group (p < 0.01). This observation was confirmed at 8 h (p < 0.001), at 24 h (p < 0.001), and finally at 48 h (p < 0.001). Loss of viability of E. coli depends on laser fluence. At 48 h, bioluminescent bacteria were not detected (100% loss of viability) in the wound irradiated at 260 J/cm2. For this fluence, the temperature reached 45 degrees C at the end of the irradiation. This study confirms previous observations on the bactericidal effect of diode lasers. Because a progressive desiccation of the superficial dermis is usually observed when using laser irradiation, the hypothesis that laser irradiation dries out the wound making the wound an inhospitable place for bacteria is much more relevant than a direct effect of infrared light on chromophores inside bacteria. This is confirmed by the fact that in this latter case, one would expect an immediate drop in luminescence followed by an increase as the surviving bacteria started to divide and repopulate the wound. However, the exact mechanism deserves further studies. This study points out the advantage of using bioluminescence imaging to evaluate laser for the treatment of acute infections in vivo, nondestructively, and noninvasively.