An Extended NIR-II Superior Imaging Window from 1500 to 1900†nm for High-Resolution In Vivo Multiplexed Imaging Based on Lanthanide Nanocrystals.

High-resolution in vivo optical multiplexing in second near-infrared window (NIR-II, 1000-1700 nm) is vital to biomedical research. Presently, limited by bio-tissue scattering, only luminescent probes located at NIR-IIb (1500-1700 nm) window can provide high-resolution in vivo multiplexed imaging. However, the number of available luminescent probes in this narrow NIR-IIb region is limited, which hampers the available multiplexed channels of in vivo imaging. To overcome the above challenges, through theoretical simulation we expanded the conventional NIR-IIb window to NIR-II long-wavelength (NIR-II-L, 1500-1900 nm) window on the basis of photon-scattering and water-absorption. We developed a series of novel lanthanide luminescent nanoprobes with emission wavelengths from 1852 nm to 2842 nm. NIR-II-L nanoprobes enabled high-resolution in vivo dynamic multiplexed imaging on blood vessels and intestines, and provided multi-channels imaging on lymph tubes, tumors and intestines. The proposed NIR-II-L probes without mutual interference are powerful tools for high-contrast in vivo multiplexed detection, which holds promise for revealing physiological process in living body.

Size-Dependent Photothermal Conversion and Photoluminescence of Theranostic NaNdF4 Nanoparticles under Excitation of Different-Wavelength Lasers.

The narrow absorption and emission bands, long fluorescence lifetime, and excellent stability of rare earth nanoparticles (referred to as RE NPs) make them very attractive for multimodal imaging and therapy of cancer. Their narrow absorption requires the careful selection of laser wavelength to achieve the best performance, particularly for RE NPs simultaneously having photothermal and photoluminescent properties (e.g., Nd-based nanoparticles), which has not been investigated. Herein, we prepared a series of different-sized NaNdF4 nanoparticles (referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from ultrasmall nanoclusters and investigated their in vitro and in vivo size-dependent photothermal conversion and photoluminescence under irradiation by a 793 nm laser and an 808 nm laser, respectively. We find that all nanoparticles exhibited the better photothermal conversion performance under the irradiation of the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF NPs showed the best performance, and the temperature of their solution can be quickly increased from 30 °C to around 60 °C within 10 min under the irradiation of the 808 nm laser with a power intensity of 0.75 W/cm2. When we used the 793 nm laser to excite these NNF NPs, we found that all nanoparticles exhibited the stronger photoluminescence in the second near-infrared window (NIR-II) than under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs possessed the strongest NIR-II luminescence. We then modified 12.8 nm NNF NPs with phospholipid carboxyl PEG and functionalized with RGD for actively targeted imaging of cancer. The NaNdF4@PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility, stability, and excellent targeting capability. The in vivo result show that 12.8 nm NNF NPs exhibited better photothermal conversion performance under the irradiation of the 808 nm laser, and stronger NIR-II fluorescence under irradiation of the 793 nm laser, which are consistent with the in vitro result. This work demonstrates the significance of selection of the proper laser wavelength for maximally taking advantage of RE nanoparticles for the diagnosis and treatment of cancer.

Dye-Sensitized Rare Earth Nanoparticles with Up/Down Conversion Luminescence for On-Demand Gas Therapy of Glioblastoma Guided by NIR-II Fluorescence Imaging.

As the primary malignant tumor in the brain, glioblastoma exhibits a high mortality due to the challenges for complete treatment by conventional therapeutic methods. It is of great importance to develop innovative therapeutic agents and methods for treatment of glioblastoma. In this work, the imaging and therapy of glioblastoma are reported by using dye sensitized core-shell NaYF4 :Yb/Tm@NaYF4 :Nd nanoparticles with strong up/down-conversion luminescence, of which the ultraviolet up-conversion emissions at 348 and 365 nm are significantly enhanced by nearly 28 times and used to control the release of SO2 from 5-Amino-1,3-dihydrobenzo[c]thiophene 2,2-dioxide prodrug for gas therapy, and the second near-infrared (NIR-II) down conversion emission at 1340 nm is increased five times and applied for imaging. It is revealed that the released SO2 molecules not only cause oxidative stress damage of tumor cells, but also induce their pro-death autophagy by down-regulating the expression of p62 and up-regulating the ratio of LC3-II/LC3-I, ultimately inhibiting tumor growth. The work demonstrates the great potential of rare earth nano-platform with functions of NIR-II imaging and photo-controlled gas therapy in the diagnosis and treatment of orthotopic glioblastoma.

Reducing Chemo-/Radioresistance to Boost the Therapeutic Efficacy against Temozolomide-Resistant Glioblastoma.

Chemo-/radioresistance is the most important reason for the failure of glioblastoma (GBM) treatment. Reversing the chemo-/radioresistance of GBM for boosting therapeutic efficacy is very challenging. Herein, we report a significant decrease in the chemo-/radioresistance of GBM by the in situ generation of SO2 within a tumor, which was released on demand from the prodrug 5-amino-1,3-dihydrobenzo[c]thiophene 2,2-dioxide (ATD) loaded on rare-earth-based scintillator nanoparticles (i.e., NaYF4:Ce@NaLuF4:Nd@ATD@DSPE-PEG5000, ScNPs) under X-ray irradiation. Our novel X-ray-responsive ScNPs efficiently converted highly penetrating X-rays into ultraviolet rays for controlling the decomposition of ATD to generate SO2, which effectively damaged the mitochondria of temozolomide-resistant U87 cells to lower the production of ATP and inhibit P-glycoprotein (P-gp) expression to reduce drug efflux. Meanwhile, the O6-methylguanine-DNA methyltransferase (MGMT) of drug-resistant tumor cells was also reduced to prevent the repair of damaged DNA and enhance cell apoptosis and the efficacy of chemo-/radiotherapy. The tumor growth was obviously suppressed, and the mice survived significantly longer than untreated temozolomide-resistant GBM-bearing mice. Our work demonstrates the potential of SO2 in reducing chemo-/radioresistance to improve the therapeutic effect against resistant tumors if it can be well controlled and in situ generated in tumor cells. It also provides insights into the rational design of stimuli-responsive drug delivery systems for the controlled release of drugs.

Synthesis, modification and bioapplications of nanoscale copper chalcogenides.

Copper chalcogenides have a simple general formula, variable atomic ratios, and complicated crystal structures, which lead to their wealth of optical, electrical, and magnetic properties with great potential for wide applications ranging from energy conversion to the biomedical field. Herein, we summarize the recent advances in (1) the synthesis of size- and morphology tunable nanostructures by different methods; (2) surface modification and functionalization for different purposes; and (3) bioapplications for diagnosis and treatment of tumors by different imaging and therapy methods, as well as antibacterial applications. We also briefly discuss the future directions and challenges of copper chalcogenide nanoparticles in the biomedical field.

Functionalization of small black phosphorus nanoparticles for targeted imaging and photothermal therapy of cancer.

Black phosphorus (BP) nanomaterials have attracted extensive attention due to their unique physical, chemical, and biological properties. In this study, small BP nanoparticles were synthesized and modified with dextran and poly(ethyleneimine) for functionalization with folic acid and cyanine 7. The functionalized BP nanoparticles exhibit excellent biocompatibility, stability, and near infrared optical properties for targeted imaging of tumors through photoacoustic imaging and near-infrared fluorescence imaging. They also display high photothermal conversion efficiency for photothermal therapy of cancer. This work demonstrates the potential of functionalized small BP nanoparticles as an emerging nanotheranostic agent for the diagnosis and treatment of cancer.