A laser free self-luminous nanosystem for photodynamic therapy of cervical cancer cells.

Photodynamic therapy is a tumor treatment strategy. However, most of the photodynamic therapies rely on laser irradiation triggering, which limits their application in deep tissues. This study designed a self-luminescent nano system, hybrid protein oxygen nanocarrier coated graphene quantum dots (GQDs@HPOC) and mesoporous silica nanoparticles coated Luminol (L@MSNs), which self-assembled into GQDs@HPOC/L@MSNs without laser irradiation. The system utilized the weak acidic environment of tumors to trigger the release of Luminol and the chemiluminescence was catalyzed by HPOC. Next CRET occurred between Luminol and GQDs, producing 1O2, which could generate photodynamic damage to cervical cancer cells without the need for external laser irradiation. The system achieved the peak uptake in primary cervical cancer cells in 3 h, and had good biosafety before self-assembly. The system could significantly kill cells at a concentration of 16 µg/ml. The system will be further applied in in vivo experiments to investigate its therapeutic ability, providing a new strategy for the clinical treatment of cervical cancer.

A dual-ratio fluorescent probe with a single excitation triple-signal to synchronously detect PTK7 and miRNA-21 for breast cancer early diagnosis.

The measurement of tumor biomarker levels is of great significance for early diagnosis of breast cancer. The combination diagnosis of multiple tumor biomarkers will significantly improve the accuracy of early diagnosis. Here, we successfully developed a dual-ratio fluorescent sensing platform for the detection of breast cancer biomarkers (PTK7, miRNA-21) using single excitation triple-signal detection. Introducing three types of fluorescence nanomaterials with narrow emission peaks and long Stokes shift as signal markers, the three peaks (430 nm, 530 nm and 640 nm) of which do not interfere with each other in fluorescence spectra under a single excitation (360 nm). The sensing platform linked aptamer (apt) modified green fluorescence quantum dots (gQDs-apt1) and aptamer modified red fluorescence quantum dots (rQDs-apt2) to Fe3O4-cDNA1 and Fe3O4-cDNA2, respectively, via base complementary pairing with aptamer molecules. When PTK7/miRNA-21 is present in the system, gQDs-apt1/rQDs-apt2 bound to the Fe3O4 MNPs surface will be released to recover fluorescence. Upon DNase I digestion of free apt1 and apt2, the target molecules will be released to bind to gQDs-apt1/rQDs-apt2 for signal amplification. After magnetic separation, PTK7 and miRNA-21 can be quantified using the fluorescence intensity ratio of gQDs with bCDs and rQDs with bCDs at a single excitation of 360 nm wavelength. This method has high sensitivity, good selectivity, and can quantify both PTK7 and miRNA-21 simultaneously with an LOD of 0.426 ng mL-1 and 0.072 nM, respectively. Additionally, the sensing platform was used for serum detection of health man and breast cancer patients with satisfactory results.

A fluorescent probe for protein tyrosine kinase 7 detection in serum and cell imaging.

Tyrosine protein kinase 7 (PTK7) is overexpressed in breast cancer, which is considered as a cancer marker for breast cancer diagnosis. Therefore, a simple fluorescent probe for PTK7 detection and cell imaging was developed. In the developed probe, Fe3O4 magnetic nanoparticles were used as the fluorescent separator, and the fluorescence of carbon dots were used as the detection signal. The probe was worked by control the configurations of the aptamer of PTK7, the aptamer would be open chains by recognition of PTK7, which bond with carbon dots and show fluorescent signal. Based on the remarkably high affinity and selectivity of aptamer for PTK7, the excellent fluorescence property of carbon dots and the outstanding magnetism of Fe3O4 magnetic nanoparticles, the developed probe showed satisfied results for PTK7 detection in serum and MCF-7 cell imaging. The probe detected PTK7 in the range of 0.2-200 ng mL-1 with a detection limit of 0.0347 ng mL-1, and successfully imaged the cancer cell expressed PTK7. The results indicate that the nano-fluorescent probe has great potential for clinical applications.

Dual-emissive ratiometric fluorescent nanosensor based on multi-nanomaterials for Ag+ determination in lake water.

In this study, a sensitive ratiometric fluorescent nanosensor was constructed using a facile one-pot method by encapsulating carbon dots (CDs) and cadmium telluride quantum dots (CdTe QDs) into the pore cavities of a metal-organic framework (ZIF-8). In this nanosensor (CD/CdTe QD@ZIF-8), the fluorescence attributed to CdTe QDs was quenched by silver ions (Ag+), and the fluorescence intensity of CDs did not change. The introduction of ZIF-8 into the system can not only adsorb Ag+ but also easily separate CDs and CdTe QDs from the matrix. The developed CD/CdTe QD@ZIF-8 composite used as a ratiometric fluorescent probe exhibited high sensitivity and selectivity towards Ag+. The working linear range was 0.1-20 µM with a limit of detection (LOD) of 1.49 nM. Finally, the proposed nanosensor was applied to determine Ag+ in lake water with satisfactory results.

Dynamics of a stochastic HBV infection model with drug therapy and immune response.

Hepatitis B is a disease that damages the liver, and its control has become a public health problem that needs to be solved urgently. In this paper, we investigate analytically and numerically the dynamics of a new stochastic HBV infection model with antiviral therapies and immune response represented by CTL cells. Through using the theory of stochastic differential equations, constructing appropriate Lyapunov functions and applying Itô's formula, we prove that the disease-free equilibrium of the stochastic HBV model is stochastically asymptotically stable in the large, which reveals that the HBV infection will be eradicated with probability one. Moreover, the asymptotic behavior of globally positive solution of the stochastic model near the endemic equilibrium of the corresponding deterministic HBV model is studied. By using the Milstein's method, we provide the numerical simulations to support the analysis results, which shows that sufficiently small noise will not change the dynamic behavior, while large noise can induce the disappearance of the infection. In addition, the effect of inhibiting virus production is more significant than that of blocking new infection to some extent, and the combination of two treatment methods may be the better way to reduce HBV infection and the concentration of free virus.

Dynamics of a stochastic HBV infection model with cell-to-cell transmission and immune response.

In this paper, considering the proven role of exosomes and the inevitable randomization within-host, we establish a hepatitis B virus (HBV) model with cell-to-cell transmission and CTL immune response from a deterministic framework to a stochastic differential equation (SDE). By introducing the reproduction number $ R_0 $, we prove that $ R_0 $ can be used to govern the stochastic dynamics of the SDE HBV model. Under certain assumptions, if $ R_{0}\leq1 $, the solution of the SDE model always fluctuates around the infection-free equilibrium of the deterministic model, which indicates that the HBV will eventually disappear almost surely; if $ R_{0} > 1 $, under extra conditions, the solution of the SDE model fluctuates around endemic equilibrium of the corresponding deterministic model, which leads to the stochastic persistence of the HBV with probability one. One of the most interesting findings is that the fluctuation amplitude is positively related to the intensity of the white noise, which can provide us some useful control strategies to regulate HBV infection dynamics.