UCNPs-based nanoreactors with ultraviolet radiation-induced effect for enhanced ferroptosis therapy of tumor.

The limitations of light source limit the clinical application of optical therapy technology. How to improve the application efficiency of radiant light has become the focus of researchers. Here, we synthesize a kind of UCNPs@PVP-GOx-PpIX-Fe3+ (UPGPF) nanoreactors with rare earth upconversion nanoparticles (UCNPs) as the substrate for the enhancement of ferroptosis effect by the synergistic starvation/photodynamic therapies. Firstly, glucose oxidase (GOx) and Fe3+ loaded in UPGPF nanoreactors are used to directly face the problems of insufficient H2O2 level in tumor tissue and low Fenton reaction efficiency. Further, UCNPs can absorb NIR light at 980 nm and convert low-energy photons into high-energy photons, thereby cleverly generating ultraviolet (UV) radiation induction in vivo, which can produce a synergistic effect of enhancing iron death. The in vivo experimental results of breast cancer model mice show that the UPGPF nanoreactors have significant anticancer effect and good biosafety. With the help of the optical conversion characteristics of UCNPs, this kind of treatment idea of building a UV radiation-induced microplatform in the tumor microenvironment, which leads to the synergistic enhancement of iron death effect, provides a promising innovative design strategy for tumor research.

Biodegradable CuMoO4 Nanodots with Multienzyme Activities for Multimodal Treatment of Tumor.

Due to their complexity and variability, tumors need to be treated with multimodal combined therapy, which requires the development of therapeutic agents that can provide multimodal therapeutic effects. Herein, CuMoO4 nanodots smaller than 10 nm that can be prepared by simple hydrothermal method are reported. These nanodots can be well dispersed in water and have good biosafety and biodegradability. Further studies show that these nanodots also present multienzyme activities, such as catalase, peroxidase and glutathione peroxidase. In addition, CuMoO4 nanodots exhibit high photothermal conversion efficiency (41%) under 1064 nm near-infrared laser irradiation. In vitro and in vivo experimental results indicate that CuMoO4 nanodots can effectively inhibit the instinctive regulation of tumor cells to oxidative stress, provide sustained treatment to achieve photothermal synergistic ferroptosis, and trigger immune responses to immunogenic cell death. It is worth mentioning that the CuMoO4 nanodots also cause cuproptosis of tumor cells. This study provides a promising nanoplatform for multimodal combined therapy of cancer.

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor.

A kind of drug-loaded nanomotors with deep penetration was developed to improve the therapeutic effect of ferroptosis on tumor. The nanomotors were constructed by co-loading hemin and ferrocene (Fc) on the surface of bowl-shaped polydopamine (PDA) nanoparticles. The near-infrared response of PDA makes the nanomotor have high tumor penetration capability. In vitro experiments show that the nanomotors can exhibit good biocompatibility, high light to heat conversion efficiency, and deep tumor permeability. It is worth noting that under the catalysis of H2O2 overexpressed in the tumor microenvironment, the Fenton-like reagents hemin and Fc loaded on the nanomotors can increase the concentration of toxic •OH. Furthermore, hemin can consume glutathione in tumor cells and trigger the up-regulation of heme oxygenase-1, which can efficiently decompose hemin to Fe2+, thus producing the Fenton reaction and causing a ferroptosis effect. Notably, thanks to the photothermal effect of PDA, it can enhance the generation of reactive oxygen species and thus intervene in the Fenton reaction process, thereby enhancing the ferroptosis effect photothermally. In vivo antitumor results show that the drug-loaded nanomotors with high penetrability showed an effective antitumor therapeutic effect.

Polydopamine nanomotors loaded indocyanine green and ferric ion for photothermal and photodynamic synergistic therapy of tumor.

The limited penetration depth of nanodrugs in the tumor and the severe hypoxia inside the tumor significantly reduce the efficacy of photothermal-photodynamic synergistic therapy (PTT-PDT). Here, we synthesized a methoxypolyethylene glycol amine (mPEG-NH2)-modified walnut-shaped polydopamine nanomotor (PDA-PEG) driven by near-infrared light (NIR). At the same time, it also loaded the photosensitizer indocyanine green (ICG) via electrostatic/hydrophobicinteractions and chelated with ferric ion (Fe3+). Under the irradiation of NIR, the asymmetry of PDA-PEG morphology led to the asymmetry of local photothermal effects and the formation of thermal gradient, which can make the nanomotor move autonomously. This ability of autonomous movement was proved to be used to improve the permeability of the nanomotor in three-dimensional (3D) tumor sphere. Fe3+ can catalyze endogenous hydrogen peroxide to produce oxygen, so as to overcome the hypoxia of tumor microenvironment and thereby generate more singlet oxygen to kill tumor cells. Animal experiments in vivo confirmed that the nanomotors had a good PTT-PDT synergistic treatment effect. The introduction of nanomotor technology has brought new ideas for cancer optical therapy.

Construction of electrochemiluminescence biosensor for monitoring of glutathione released by living cancer cells.

Abnormal glutathione (GSH) levels are directly related to specific diseases. Therefore, the highly sensitive detection of GSH has attracted extensive attention of researchers. Here, we reported a novel electrochemiluminescence (ECL) biosensor platform based on AgGaS2 quantum dots (AGS QDs) for sensitive detection of GSH released by living cancer cells. Firstly, the preparation and photoluminescence of AGS QDs were studied. Then, ECL biosensor based on AGS QDs was constructed and applied to the detection of GSH released by MCF-7 cells. The experimental results showed that the ECL biosensor can sensitively detect GSH directly released by living cancer cells in situ. This work not only provides a promising choice for developing ECL with low toxicity and good biocompatibility, but also can be extended to detect other molecules released by cells, which is conducive to the in-depth study of pathophysiology.

Construction of a matchstick-shaped Au@ZnO@SiO2-ICG Janus nanomotor for light-triggered synergistic antibacterial therapy.

The drug-resistance of bacteria poses a serious threat to public health, so the exploration of new antibacterial materials has attracted extensive attention. Here, we report Au@ZnO@SiO2-ICG nanomotors as an antibacterial candidate. Firstly, we prepared the Janus structure Au@ZnO loaded with indocyanine green (ICG) and constructed a synergistic antibacterial platform with photothermal and photodynamic properties triggered by dual light sources. Specifically, the metal/semiconductor heterostructure of Au@ZnO has a synergistic effect under ultraviolet (UV) irradiation, which can adjust the transfer of interface electrons, so as to greatly improve the generation of cytotoxic ROS for photodynamic sterilization. The loaded ICG is an effective photosensitizer, and can induce a stronger photothermal effect in collaboration with Au under near-infrared light (NIR). In addition, the asymmetric structures of nanomotors have autonomous movement with the help of generated temperature gradient when exposed to NIR light, conducive to breaking through the bacterial membrane and improving the membrane insertion ability of antibacterial therapeutic agents. The results indicate that the prepared Au@ZnO@SiO2-ICG nanomotors show excellent light responses and synergistic sterilization ability to Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). This study will provide a new idea for the application of metal-semiconductor nanocomposites in the treatment of bacterial infection.

An electrochemiluminescence cytosensor for sensitive detection of HeLa cells based on a signal amplification strategy of Au-NaYF4:Yb,Er nanocomposites.

A novel electrochemiluminescence (ECL) cytosensor was proposed for the quantitative detection of HeLa cells (human cervical cancer cells) with the help of a signal amplification strategy. Firstly, the Au-NaYF4:Yb,Er nanocomposites were prepared by a simple in situ hydrothermal method and characterized by transmission electron microscopy (TEM) images, X-ray diffraction (XRD) patterns, UV-vis spectra and Fourier transform infrared (FTIR) spectra. Compared with the bare NaYF4:Yb,Er nanocomposites, the ECL intensity of Au-NaYF4:Yb,Er nanocomposites was greatly enhanced by about 4.2-fold which can be attributed to the good conductivity of gold nanoparticles (Au NPs). The nanocomposites showed high and stable ECL emission, fast response and superior conductivity, all of which were advantageous to the ECL detection. Furthermore, HeLa cells were immobilized on the modified electrode via the interaction between folic acid and a folate receptor present on the cell surface. The ECL cytosensor showed satisfactory sensitive response to HeLa cells in a linear range of 4.25 × 102-4.25 × 105 cells per mL with a low detection limit of 326 cells per mL. The proposed cytosensor had good sensitivity and stability, which can offer a great potential platform for bioassay analysis.

Facile synthesis of highly monodisperse EuSe nanocubes with size-dependent optical/magnetic properties and their electrochemiluminescence performance.

We reported a facile and robust method for the synthesis of highly monodisperse EuSe nanocubes (EuSe NCs) with controllable edge lengths in the range of 8-70 nm. The EuSe NCs were formed through the aggregation of EuSe small particles (cores) and then their surface reconstruction under the influence of 1-dodecanethiol (DDT) that acted as a capping surfactant. DDT was not only found to be critical to the nucleation temperature of preparing EuSe NCs, but also played a decisive role in the formation of structurally well-defined nanocubes. The results indicated that the remarkable monodispersity and high shape consistency of EuSe NCs were highly controlled by the change in the DDT concentration. Furthermore, the size-dependent optical/magnetic properties based on the quantum size effect and the influence of edge lengths of EuSe NCs were also investigated and discussed. More importantly, the electrochemiluminescence (ECL) performance of EuSe NCs was first reported. This will make possible more biomedical applications in future.

NaEuF4/Au@Ag2S nanoparticles-based fluorescence resonant transfer DNA sensor for ultrasensitive detection of DNA energy.

The work investigates a new fluorescence resonance energy transfer (FRET) system using NaEuF4 nanoparticles (NPs) and Au@Ag2S NPs as the energy donor-acceptor pair for the first time. The NaEuF4/Au@Ag2S NPs-based FRET DNA sensor was constructed with NaEuF4 NPs as the fluorescence (FL) donor and Au@Ag2S core-shell NPs as FL acceptor. In order to find the matching energy acceptor, the amount of AgNO3 and Na2S were controlled in the synthesis process to overlap the absorption spectrum of energy acceptor with the emission spectrum of energy donors. The sensitivity of FRET-based DNA sensor can be enhanced and the self-absorption of ligand as well as the background of signals can be decreased because of Eu3+ which owns large Stokes shifts and narrow emission bands due to f-f electronic transitions of 4f shell. We obtained the efficient FRET system by studying suitable distance between the donor and acceptor. Then the FRET-based DNA sensor was used for the design of specific and sensitive detection of target DNA and the quenching efficiency (ΔFL/F0, ΔFL=F-F0) of FL was logarithmically related to the concentration of the target DNA, ranging from 100aM to 100pM. We can realize an ultrasensitive detection of target DNA with a detection limit of 32 aM. This proposed method was feasible to analyse target DNA in real samples with satisfactory results.