NIR II Luminescence Imaging for Sentinel Lymph Node and Enhanced Chemo-/Photothermal Therapy for Breast Cancer

In this research, a NIR II luminescence imaging and enhanced chemo-/photothermal therapy system of CuS–DOX–Nd/FA NPs for breast cancer and lymph node tracing under single 808 nm irradiation is proposed. Nd–DTPA molecular cluster with the NIR II imaging effect as the carrier was designed to load the ultrasmall CuS nanoparticles and chemotherapeutic drug doxorubicin hydrochloride (DOX). The composite probe is used for tumor lesion imaging and tracking the breast cancer sentinel lymph nodes with simultaneous chemo-/photothermal therapy (PTT) for breast cancer under the single 808 nm laser. This designed probe not only has high permeability and retention (EPR) targeting effect but also can respond to the tumor microenvironment (TME), realizing more precise and efficient release of DOX at the cancer focus. At the same time, CuS as a drug carrier has a good photothermal therapy effect (photothermal conversion efficiency: 27.9%). The serialized released chemotherapy DOX and synergistic PTT effect can be used to the treat the in situ breast cancer land and simultaneously kill the metastasis cancer. The system made the combined molecular clusters Nd–DTPA achieve NIR II imaging of tumor lesions of breast cancer and lymph node to obtain the integration of diagnosis of the transferred disease for better prognosis. The feasibility of the system had obvious tumor growth inhibition effect with NIR II imaging guided is verified by a series of in vitro and in vivo experiments

Lanthanide-Based Nanocomposites for Photothermal Therapy under Near-Infrared Laser: Relationship between Light and Heat, Biostability, and Reaction Temperature

In this research, typical organic/inorganic photothermal therapy (PTT) agents were designed with a combination of upconversion luminescent (UCL) or near-infrared (NIR) II imaging rare-earth nanomaterials for photo-acoustic (PA)/UCL/NIR II imaging-guided PTT under NIR laser irradiation. The results show the following: (1) The PTT effect mainly comes from NIR absorption and partly from UCL light conversion. (2) Visible UCL emission is mainly quenched by NIR absorption of the coated PTT agent and partly quenched by visible absorption, indicating that excitation may play a more important role than in the UCL emission process. (3) The biostability of the composite might be decided by the synthesis reaction temperature. Among the five inorganic/organic nanocomposites, UCNP@MnO2 is the most suitable candidate for cancer diagnosis and treatment because of its stimuli-response ability to the micro-acid environment of tumor cells and highest biostability. The composites generate heat for PTT after entering the tumor cells, and then, the visible light emission gradually regains as MnO2 is reduced to colorless Mn2+ ions, thereby illuminating the cancer cells after the therapy

Highly Uniform Hollow GdF₃ Spheres: Controllable Synthesis, Tuned Luminescence, and Drug-Release Properties

In this paper, uniform hollow mesoporous GdF3 micro/nanospheres were successfully prepared by a facile two-step synthesis route without using any surfactant, catalyst, and further calcination process. The precursor Gd­(OH)­CO3 spheres are prepared by a coprecipitation process. After that, uniform and size-tunable GdF3 hollow spheres were easily coprecipitated with NaBF4 at the sacrifice of the precursor with low temperature and short reaction time. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution TEM, N2 adsorption/desorption, and up-conversion (UC) photoluminescence spectra were used to characterize the as-obtained products. It is found that the initial pH value and NaBF4/Gd3+ molar ratios play important roles in the structures, sizes, and phases of the hollow products. The growth mechanism of the hollow spheres has been systematically investigated based on the Kirkendall effect. Under 980 nm IR laser excitation, UC luminescence of the as-prepared Yb3+/Er3+-codoped GdF3 hollow spheres can be changed by a simple adjustment of the concentration of the Yb3+ ion. Enhanced red emission is obtained by introducing Li+ ions in GdF3:Yb3+/Er3+. Furthermore, a doxorubicin release experiment and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay reveal that the product has potential application in drug delivery and targeted cancer therapy

Surfactant-Free Synthesis, Luminescent Properties, and Drug-Release Properties of LaF₃ and LaCO₃F Hollow Microspheres

Uniform LaF3 and LaCO3F hollow microspheres were successfully synthesized through a surfactant-free route by employing La­(OH)­CO3 colloidal microspheres as a sacrificial template and NaBF4 as the fluorine source. The synthetic process consists of two steps: the preparation of a La­(OH)­CO3 precursor via a facile urea-based precipitation and the following formation of lanthanide fluoride hollow microspheres under aqueous conditions at low temperature (50 °C) and short reaction time (3 h), without using any surfactant and catalyst. The formation of hollow spheres with controlled size can be assigned to the Kirkendall effect. It is found that the phase and structure of the products can be simply tuned by changing the pH values of the solution. Time-dependent experiments were employed to study the possible formation process. N2 adsorption/desorption results indicate the mesoporous nature of LaF3 hollow spheres. Yb3+/Er3+ (Ho3+) and Yb3+/Tm3+-doped LaF3 hollow spheres exhibit characteristic up-conversion (UC) emissions of Er3+ (Ho3+) and Tm3+ under 980 nm laser-diode excitation, and Ce3+/Tb3+-doped LaF3 and LaCO3F emit bright yellow-green and near-white light under UV irradiation, respectively. In particular, LaF3:Yb/Er and LaCO3F:Ce/Tb hollow microspheres exhibit obvious sustained and pH-dependent doxorubicin release properties. The luminescent properties of the carriers allow them to be tracked or monitored during the release or therapy process, suggesting their high potential in the biomedical field

Hollow Structured Y₂O₃:Yb/Er–Cu_<i>x</i>S Nanospheres with Controllable Size for Simultaneous Chemo/Photothermal Therapy and Bioimaging

To integrate photothermal therapy (PTT) with chemotherapy for improved antitumor efficiency, we designed a novel multifunctional composite by attaching Cu_<i>x</i>S nanoparticles onto the surface of Y₂O₃:Yb/Er hollow spheres through a combined coprecipitation and subsequent hydrothermal route. By altering the initial pH values for the synthesis of precursors, the size and structure properties of the final composites can controllably be tuned. The conjugated folic acid (FA) makes the composite recognize the targeted cancer cells and the attached Cu_<i>x</i>S nanoparticles endow the composite with photothermal function. It is found that the release of doxorubicin (DOX) from the functional carrier could be triggered by both pH value and near-infrared (NIR) radiation. In particular, both PTT and chemotherapy can be simultaneously driven by 980 nm laser irradiation. The synergistic therapeutic effect based on PTT and chemotherapy can lead to low in vitro viability of 12.9% and highly strong inhibition of animal H22 tumor in vivo, which is superior to any individual therapy. Moreover, the composite exhibits the clear in vivo red up-conversion luminescence (UCL). This multifunctional nanocarrier can be applicable as bioimaging agent and effective antitumor agent for the synergistic interaction between PTT and the enhanced chemotherapy

Fluorescence-Recovered Wearable Hydrogel Patch for In Vitro Detection of Glucose Based on Rare-Earth Nanoparticles

The physiological state of the human body can be indicated by analyzing the composition of sweat. In this research, a fluorescence-recovered wearable hydrogel patch has been designed and realized which can noninvasively monitor the glucose concentration in human sweat. Rare-earth nanoparticles (RENPs) of NaGdF4 doped with different elements (Yb, Er, and Ce) are synthesized and optimized for better luminescence in the near-infrared second (NIR-II) and visible region. In addition, RENPs are coated with CoOOH of which the absorbance has an extensive peak in the visible and NIR regions. The concentration of H2O2 in the environment can be detected by the fluorescence recovery degree of CoOOH-modified RENPs based on the fluorescence resonance energy transfer effect. For in vivo detection, the physiological state of oxidative stress at tumor sites can be visualized through its fluorescence in NIR-II with low background noise and high penetration depth. For the in vitro detection, CoOOH-modified RENP and glucose oxidase (GOx) were doped into a polyacrylamide hydrogel, and a patch that can emit green upconversion fluorescence under a 980 nm laser was prepared. Compared with the conventional electrochemical detection method, the fluorescence we presented has higher sensitivity and linear detection region to detect the glucose. This improved anti-interference sweat patch that can work in the dark environment was obtained, and the physiological state of the human body is conveniently monitored, which provides a new facile and convenient method to monitor the sweat status

Optimization of Red Luminescent Intensity in Eu3+-Doped Lanthanide Phosphors Using Genetic Algorithm

In this research, four steps including synthesis experiment, brightness evaluation, optimized calculation using brightness as fitness reference, and new calculated composition for the next preparation have been proceeded to find the brightest Eu3+ doped phosphors combined with chemical experiments and genetic algorithm (GA) calculation. The evolutionary operations, such as elitism, selection, crossover, and mutation, are applied to the compound combination. Feasible optimized combination would be obtained until the phosphor is found to be satisfactory. Through GA calculation and thd experimental process, the final luminescence enhancement factor of the optimal phosphor is up to 141% compared with the best one in the first generation. Thus, the GA calculation could be well applied to combinatorial chemistry to find the better phosphor. Additionally, the optimized phosphor is potentially applied as the fingerprint detection nanoparticle and dual-modal imaging agent of the CT/luminescent agent with high penetration and resolution

Surface Plasmonic Enhanced Imaging-Guided Photothermal/Photodynamic Therapy Based on Lanthanide–Metal Nanocomposites under Single 808 nm Laser

In this research, we design the integration of Au/Ag nanocages with upconversion nanoparticles (UCNPs) as the theranostic agent under single 808 nm with enhanced imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) properties. Different with the conventional theranostic agent, Au/Ag@UCNPs can emit higher blue emission under 808 nm laser and generate higher reactive oxygen species than that of Au@UCNPs due to higher crossed absorbance between the nanocages and UCNPs. Furthermore, the temperature change of Au/Ag@UCNPs (9.7 °C) is much higher than that of phosphate-buffered saline solution (0.6 °C) under 808 nm laser, indicating there is a low side effect to normal cells when Au/Ag@UCNPs are utilized as the photoactive agent. Finally, the in vitro and in vivo experiments show that the tumor is almost ablated totally due to high synergistic PDT and PTT effects of Au/Ag@UCNPs, revealing it could be potentially applied in the clinical theranostic field

Multilevel Nanoarchitecture Exhibiting Biosensing for Cancer Diagnostics by Dual-Modal Switching of Optical and Magnetic Resonance Signals

In this research, the fabrication and application of a multifunctional core–shell nanoarchitecture are proposed. NaYF4:Yb,Er@NaYF4:Yb,Nd exhibits upconversion luminescence (UCL) of erbium ions but has quenched UCL emission when it is coated with MnO2 nanosheets. This hierarchical multilevel UCNP-MnO2 exhibits restoration of UCL and generation of a magnetic resonance imaging (MRI) signal when it is exposed to a microenvironment containing glutathione (GSH)/H2O2, which strips the MnO2 sheets by converting them to paramagnetic Mn2+ ions. This dual-modal switching feature of the optical emission and MRI signals provides a platform for stimuli-responsive biosensing of GSH/H2O2. Our new formulation as a dual-modal biosensor for detecting aberrant levels of intracellular GSH/H2O2 associated in cancer cells could be a potential diagnostic probe to distinguish tumor cells from normal cells