Integration of Au Nanosheets and GdOF:Yb,Er for NIR‑I and NIR-II Light-Activated Synergistic Theranostics

The local hyperthermia (>41 °C) effect of photothermal therapy (PTT) is significantly limited by the efficiency of PTT agents to convert laser energy to heat, and such oncotherapy, similar to conventional chemotherapy, invariably encounters the challenge of nonspecific application. Undue reliance on oxygen sources still poses particular difficulties in photodynamic therapy (PDT) for deep-level clinical applications. Considering these therapeutic issues, in this study, we constructed a versatile but unique nanosystem by encapsulating Au nanosheets in codoped gadolinium oxyfluoride (GdOF):Yb,Er spheres, followed by decoration of a chemotherapeutic drug (doxorubicin), photosensitizer (rose Bengal, RB), and targeted agent (folic acid). This allowed the incorporation of cancer treatment and real-time curative efficacy monitoring into one single theranostic nanoplatform. Benefiting from the dual contribution of the strong absorptions in the NIR-I and NIR-II regions, relevant photothermal-conversion efficiency (η) values pertaining to that final product were 39.2% at 1064 nm irradiation and 35.7% at 980 nm illumination. The fluorescence resonance energy transfer that occurred in the up-converted GdOF:Yb,Er to RB contributed to the high PDT efficacy. Combined with a micromeric acid-responsive drug release in a targeted tumor microenvironment, high-performance synergistic therapy was realized. In addition, up-conversion fluorescence imaging and computed tomography imaging accompanied by multimodal magnetic resonance imaging were simultaneously achieved owing to the doped lanthanide ions and the encapsulated Au nanosheets. Our designed oncotherapy nanosystem provides an alternative strategy to acquire ideal theranostic effects

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

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

Multifunctional Theranostics for Dual-Modal Photodynamic Synergistic Therapy via Stepwise Water Splitting

Combined therapy using multiple approaches has been demonstrated to be a promising route for cancer therapy. To achieve enhanced antiproliferation efficacy under hypoxic condition, here we report a novel hybrid system by integrating dual-model photodynamic therapies (dual-PDT) in one system. First, we attached core–shell structured up-conversion nanoparticles (UCNPs, NaGdF₄:Yb,Tm@NaGdF₄) on graphitic-phase carbon nitride (<i>g-</i>C₃N₄) nanosheets (one photosensitizer). Then, the as-fabricated nanocomposite and carbon dots (another photosensitizer) were assembled in ZIF-8 metal–organic frameworks through an in situ growth process, realizing the dual-photosensitizer hybrid system employed for PDT via stepwise water splitting. In this system, the UCNPs can convert deep-penetration and low-energy near-infrared light to higher-energy ultraviolet–visible emission, which matches well with the absorption range of the photosensitizers for reactive oxygen species (ROS) generation without sacrificing its efficacy under ZIF-8 shell protection. Furthermore, the UV light emitted from UCNPs allows successive activation of <i>g</i>-C₃N₄ and carbon dots, and the visible light from carbon dots upon UV light excitation once again activate <i>g</i>-C₃N₄ to produce ROS, which keeps the principle of energy conservation thus achieving maximized use of the light. This dual-PDT system exhibits excellent antitumor efficiency superior to any single modality, verified vividly by in vitro and in vivo assay

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

Near-Infrared Upconversion Mesoporous Tin Dioxide Theranostic Nanocapsules for Synergetic Cancer Chemophototherapy

Smart nanotheranostic systems (SNSs) have attracted extensive attention in antitumor therapy. Nevertheless, constructing SNSs with disease diagnosis ability, improved drug delivery efficiency, inherent imaging performance, and high treatment efficiency remains a scientific challenge. Herein, ultrasmall tin dioxide (SnO2) was assembled with upconversion nanoparticles (UCNPs) to form mesoporous nanocapsules by an in situ hydrothermal deposition method, followed by loading with doxorubicin (DOX) and modification with bovine serum albumin (BSA). pH/near-infrared dual-responsive nanotheranostics was constructed for computed tomography (CT) and magnetic resonance (MR) imaging-induced collaborative cancer treatment. The mesoporous channel of SnO2 was utilized as a reservoir to encapsulate DOX, an antineoplastic drug, for chemotherapy and as a semiconductor photosensitizer for photodynamic therapy (PDT). Furthermore, the DOX-loaded UCNPs@SnO2-BSA nanocapsules combined PDT, Nd3+-doped UCNP-triggered hyperthermia effect, and DOX-triggered chemotherapy simultaneously and demonstrated prominently enhanced treatment efficiency compared to the monotherapy model. Moreover, tin, as one of the trace elements in the human body, has a similar X-ray attenuation coefficient to iodine and therefore can act as a contrast agent for CT imaging to monitor the treatment process. Such an orchestrated synergistic anticancer treatment exhibited apparent inhibition of tumor growth in tumor-bearing mice with negligible side effects. Our study demonstrates nanocapsules with excellent biocompatibility and great potential for cancer treatment

Lutecium Fluoride Hollow Mesoporous Spheres with Enhanced Up-Conversion Luminescent Bioimaging and Light-Triggered Drug Release by Gold Nanocrystals

Uniform Na₅Lu₉F₃₂ hollow mesoporous spheres (HMSs) have been successfully prepared by a facile and mild (50 °C for 5 h) coprecipitation process, and Au nanocrystals (NCs) with particle size of about 10 nm were conjugated to poly­(ether imide) (PEI) modified HMSs by electrostatic interaction. Compared with Na₅Lu₉F₃₂:Yb/Er HMSs, the up-conversion (UC) luminescence intensity of Na₅Lu₉F₃₂:Yb/Er@Au HMSs was much higher under low pump power due to the local field enhancement (LFE) of Au NCs, and there is a surface plasmon resonance (SPR) effect with nonradiative transitions which generates a thermal effect. These two effects have been proved by theoretical discrete-dipole approximation (DDA) simulation. The good biocompatibility of Na₅Lu₉F₃₂:Yb/Er@Au HMSs indicates them as a promising candidate in the biological field. Particularly, under near-infrared (NIR) laser irradiation, a rapid doxorubicin (DOX) release was achieved due to the thermal effect of Au NCs. In this case, Na₅Lu₉F₃₂:Yb/Er@Au HMSs exhibit an apparent NIR light-controlled “on/off” drug release pattern. In addition, UC luminescent images uptaken by cells show brighter green and red emission under NIR laser excitation. Therefore, this novel multifunctional (mesoporous, enhanced UC luminescent, and light-triggered drug release) material should be potential as a suitable targeted cancer therapy carrier and bioimaging

On-Demand Triggered Chemodynamic Therapy by NIR-II Light on Oxidation-Prevented Bismuth Nanodots

As the least toxic heavy metal, monoelemental bismuth nanomaterials with several superiorities are the ideal theranostic agents. However, bismuth nanoparticles are easily oxidized by oxygen in air or media, limiting their clinical application. In contrast, the oxidization of Bi0 to Bi3+ can activate the chemodynamic therapy (CDT) by transferring endogenous H2O2 into •OH. Herein, a well-designed Bi-DMSNs@PCM nanosystem was prepared via in situ growth of Bi nanodots and a coating of phase-change material (PCM) on the surface of dendritic mesoporous silica nanoparticles (DMSNs). The coated PCM protects the Bi nanodots from oxidation by keeping them in the Bi0 state for more than 15 d. When irradiated using the near infrared-II (NIR-II) laser with a low power density (0.5 W/cm2), the heat generated from the Bi nanodots melts the PCM shell to trigger CDT through a Fenton-like reaction, accompanied by heat-induced photothermal therapy (PTT). Notably, the CDT can also compensate for the reduced PTT effect caused by the oxidation of Bi nanodots, and a satisfactory treatment effect is realized. Additionally, photoacoustic and computed tomography imaging properties were obtained. Our strategy transfers the detrimental self-oxidation of bismuth to a beneficial therapeutic mode, enhancing the potential of Bi for clinical use

La(OH)₃:Ln³⁺ and La₂O₃:Ln³⁺ (Ln = Yb/Er, Yb/Tm, Yb/Ho) Microrods: Synthesis and Up-conversion Luminescence Properties

One-dimensional La­(OH)₃:Ln³⁺ (Ln = Yb/Er, Yb/Tm, Yb/Ho) microrods have been successfully synthesized using molten composite-hydroxide (NaOH/KOH) as a solvent. La₂O₃:Ln³⁺ nanostructures with retained striplike shape were achieved by a subsequent annealing process. The phase, structure, morphology, and fluorescent properties have been well investigated by various techniques. It is found that the reaction time plays a key role in confining the growth of the microrods. Both La­(OH)₃:Ln³⁺ and La₂O₃:Ln³⁺ nanostructures have rodlike shapes with a typical width of 50–400 nm. The up-conversion (UC) photoluminescence (PL) properties of the samples have been studied in detail. Under 980 nm laser excitation, both La­(OH)₃:Ln³⁺ and La₂O₃:Ln³⁺ microrods exhibit the characteristic emissions of Er³⁺, Tm³⁺, and Ho³⁺ and give green, blue, and blackish green emission colors, respectively. Additionally, the doping concentration of Yb³⁺ has been optimized by fixing the Er³⁺ concentration. It should be noted that the up-conversion emission of La₂O₃:Er³⁺ microrods can be significantly improved in comparison with that of their bulk counterpart under the same excitation conditions