BACKGROUND: Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm-HSA-ICG-PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts.
RESULTS: The size of the CCm-HSA-ICG-PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm-HSA-ICG-PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm-HSA-ICG-PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm-HSA-ICG-PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm-HSA-ICG-PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm-HSA-ICG-PFTBA till 14 days.
CONCLUSIONS: By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm-HSA-ICG-PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.

Mitochondria-lysosome interactions are essential for maintaining intracellular homeostasis. Although various fluorescent probes have been developed to visualize such interactions, they remain unable to label mitochondria and lysosomes simultaneously and dynamically track their interaction. Here, we introduce a cell-permeable, biocompatible, viscosity-responsive, small organic molecular probe, Coupa, to monitor the interaction of mitochondria and lysosomes in living cells. Through a functional fluorescence conversion, Coupa can simultaneously label mitochondria with blue fluorescence and lysosomes with red fluorescence, and the correlation between the red-blue fluorescence intensity indicates the progress of mitochondria-lysosome interplay during mitophagy. Moreover, because its fluorescence is sensitive to viscosity, Coupa allowed us to precisely localize sites of mitochondria-lysosome contact and reveal increases in local viscosity on mitochondria associated with mitochondria-lysosome contact. Thus, our probe represents an attractive tool for the localization and dynamic tracking of functional mitochondria-lysosome interactions in living cells.

Hepatitis B is a globally prevalent viral infectious disease caused by the hepatitis B virus (HBV). In this study, an immunochromatographic assay (ICA) for the rapid detection of hepatitis B preS2 antigen (preS2Ag) was established. The magnetic nanoparticles (MNPs) indirectly labelled with goat anti-mouse (GAM) secondary antibody were applied as a nanoprobe for free preS2 antibody (preS2Ab) capturing and signal amplification. By employing sample pre-incubation processing as well, preS2Ag-preS2Ab was sufficiently caught by the GAM-MNPs probe in 5 min. A qualitative sensitivity of 625 ng/mL was obtained by naked-eye observation within 15-20 min. A standard curve (0-5000 ng/mL) was established, with a quantitative limit of detection (LOD) of 3.6 ng/mL, based on the stability and penetrability of the magnetic signal characteristics. The proposed method for preS2Ag was rapid (~25 min, cf. ELISA ~4 h) and had a good accuracy, which was verified using an ELISA kit (relative error < 15%). Large equipment and skilled technicians were not required. The sensitivity and specificity of the developed GAM-MNPs-ICA method were 93.3% and 90% in clinical serum samples (n = 25), respectively. A good detection consistency (84%) was observed between the developed ICA method and 2 types of commercial ELISA kits, indicating that the GAM-MNPs-ICA has a potential application in large-scale screening for and point-of-care diagnosis of hepatitis B or other infectious diseases.

Microbially mediated decomposition of particulate organic carbon (POC) is a central component of the oceanic carbon cycle, controlling the flux of organic carbon from the surface ocean to the deep ocean. Yet, the specific microbial taxa responsible for POC decomposition and degradation in the deep ocean are still unknown. To target the active microbial lineages involved in these processes, 13 C-labeled particulate organic matter (POM) was used as a substrate to incubate particle-attached (PAM) and free-living microbial (FLM) assemblages from the epi- and bathypelagic zones of the New Britain Trench (NBT). By combining DNA stable-isotope probing and Illumina Miseq high-throughput sequencing of bacterial 16S rRNA gene, we identified 14 active bacterial taxonomic groups that implicated in the decomposition of 13 C-labeled POM at low and high pressures under the temperature of 15°C. Our results show that both PAM and FLM were able to decompose POC and assimilate the released DOC. However, similar bacterial taxa in both the PAM and FLM assemblages were involved in POC decomposition and DOC degradation, suggesting the decoupling between microbial lifestyles and ecological functions. Microbial decomposition of POC and degradation of DOC were accomplished primarily by particle-attached bacteria at atmospheric pressure and by free-living bacteria at high pressures. Overall, the POC degradation rates were higher at atmospheric pressure (0.1 MPa) than at high pressures (20 and 40 MPa) under 15°C. Our results provide direct evidence linking the specific particle-attached and free-living bacterial lineages to decomposition and degradation of diatomic detritus at low and high pressures and identified the potential mediators of POC fluxes in the epi- and bathypelagic zones.

Near-infrared (NIR) fluorescence imaging has been proved as an effective modality in identifying the tumor border and distinguishing the tumor cells from healthy tissue during the oncological surgery. Developing NIR fluorescent probes with high tumor to background (T/B) signal is essential for the complete debulking of the tumor, which will prolong the survival rate of tumor patients. However, the nonspecific binding and \"always-on\" properties of the conventional fluorescent probes leads to high background signals and poor specificity. Method: To address this problem, glutathione (GSH)-responsive, two disulfide-bonded dicyanine dyes (ss-diCy5 and ss-diNH800CW) were synthesized. As synthesized dyes are quenched under normal physiological conditions, however, once reached to the tumor site, these dyes are capable of emitting strong fluorescence signals primarily because of the cleavage of the disulfide bond in the tumor microenvironment with high GSH concentration. Besides, the GSH-responsive behavior of these dyes was monitored using the UV-vis and fluorescence spectroscopy. The diagnostic accuracy of the aforementioned dyes was also tested both in tumor cells and 4T1-bearing mice. Results: The fluorescence signal intensity of disulfide dicyanine dyes was quenched up to 89% compared to the mono cyanine dyes, thus providing a very low fluorescence background. However, when the disulfide dicyanine dye reaches the tumor site, the dicyanine is cleaved by GSH into two mono-dyes with high fluorescence strength, thus producing strong fluorescent signals upon excitation. The fluorescent signal of the dicyanine was enhanced by up to 27-fold after interacting with the GSH solution. In vivo xenografts tumor studies further revealed that the fluorescence signals of aforementioned dyes can be quickly recovered in the solid tumor. Conclusion: In summary, the disulfide dicyanines dyes can provide a promising platform for specific tumor-activatable fluorescence imaging with improved T/B value.

Highly catalytic and stable N-doped carbon dots (N-CDs) were prepared rapidly by microwave procedure using glucose as precursor and ammonium sulfite as N-dopant. The reduction of AgNO3 by trisodium citrate (TCA) was slow to form nanosilver (AgNP), and the N-CDs exhibited strong catalysis of the AgNP reaction. The formed AgNPs were used as indicator in the presence of Vitoria blue B (VBB) molecule probe with a SERS peak at 1615 cm-1. With the increase of nancatalyst N-CDs concentration, the AgNP reaction speed up, and the SERS peak of VBB enhanced linearly due to formation of more AgNPs as substrate. In the presence of avidin (Ad), the SERS peak weakened. Upon addition of biotin, the SERS peak enhanced due to turn on the indicator nanoreaction. The enhanced SERS signal had a good linear relationship with the biotin concentration in range of 0.0006-0.021 ng/mL, with a detection limit of 0.3 pg/mL.

The feasibility and efficacy of magnetic resonance imaging molecular probe application and pluripotent stem cell-derived neural stem cell (NSC) transplantation for the treatment of hind limb paralysis in mice with cerebral infarction were studied. A model of middle cerebral artery infarction using adult mice was established to stimulate hind limb reactions. After the model was successfully established, the mice were first divided into an experimental group and a control group, with 25 mice in each group. Cultured neural cells were obtained from the cerebral cortex and hippocampus of a mouse 15 days pregnant to prepare pluripotent stem cells. Pluripotent stem cell-derived NSCs were identified by positive expression of Nestin. The experimental group was injected with 1 μL of NSC suspension through the tail vein, and the control group was injected with 1 μL of saline through the tail vein. The neurologic function of mice in each group was scored 1 day, 3 days, 7 days, 14 days, and 28 days after transplantation according to the Garcia 18 subscale. Finally, the differentiation, migration, and integration of pluripotent stem cell-derived NSCs after transplantation were observed using a magnetic resonance imaging molecular probe method. The results showed that the neurologic function scores of the ischemic transplantation group were significantly higher than those of the control group, and the results were significantly different (P < 0.05). Through research, it was found that after transplantation of pluripotent stem cell-derived NSCs, the transplanted cells migrated and differentiated around the body at 28 days and participated in angiogenesis, and the blood vessels in the infarcted area were obviously proliferated. The NSCs cultured in vitro were transplanted to the small infarction after cerebral infarction. In rats, it plays a positive role in the repair of nerve function in mice with cerebral infarction. NSCs cultured in vitro can survive, migrate, and differentiate in the brain tissue of mouse ischemic models and play a positive role in the repair of neurologic function in mice with cerebral infarction. Magnetic resonance imaging molecular probes have a good adjuvant effect on the use of pluripotent stem cell-derived NSCs to treat hind limb paralysis in mice with cerebral infarction.

This paper used magnetic resonance diffusion kurtosis imaging to observe the acute cerebral infarction model of mice, and studied the imaging changes of ischemic penumbra after perfusion of model for rat middle cerebral artery occlusion experiment, and combined with the physiologic changes of mice. The damage of neurons was evaluated by the evolution of N-methyl-D-aspartate receptors to provide a corresponding imaging basis for the diagnosis and treatment of ischemic penumbra. The research shows that the diffusivity value decreases with time, and the diffusion kurtosis increases with time. The difference in diffusivity between different parts of the same time point and the same part of the same point (except the edge relative to the normal area) is statistically different. Learning significance was set at P < 0.05. The expression of N-methyl-D-aspartate receptor 2A in tissue homogenate increased overall, and expression in synaptic membrane, synaptic membrane, and light membrane decreased. The expression of N-methyl-D-aspartate acid receptor 2B in tissue homogenate, synaptic membrane, and light cell membrane decreased, and it increased first and then decreased in the synaptic membrane. The studies confirmed that magnetic resonance imaging has a certain clinical diagnostic value for the penumbra evolution mechanism and neuronal injury of acute cerebral infarction, which deserves further study.

Different from fluorescent dyes-doped or carbon materials-based ratiometric tetracycline nanoprobes, herein, a new Ir(III) complex-doped and europium(III) ion (Eu3+)-functionalized silicon nanoparticles (Ir(III)@SiNPs-Eu3+) with long luminescent lifetimes was firstly fabricated for selective detection of tetracycline (TC) in complex systems through time-resolved emission spectra (TRES) measurement. In the presence of TC, the red phosphorescence of Eu3+ is greatly enhanced by adsorption energy transfer emission (AETE) of TC, while the strong green luminescence of Ir(III)@SiNPs is quenched by the inner filtration effect (IFE) of TC. Based on these striking emission changes, Ir(III)@SiNPs-Eu3+ can sensitively detect TC in the linear range of 0.01-20 μM with a detection limit of 4.9 × 10-3 μM. Benefitting from the long lifetime of Ir(III)@SiNPs-Eu3+, the nanoprobe demonstrates excellent TC detection performance through TRES in high background system of 5 % human serum. Furthermore, the formed Ir(III)@SiNPs-Eu3+/TC complex can be used to sensitively recognize Hg2+ via a ratiometric luminescence mode. Notably, the cytotoxicity of Ir(III)@SiNPs-Eu3+ is very low and thus the sensitive monitoring the detection of Ir(III)@SiNPs-Eu3+ to TC and Hg2+ also works well in porcine renal cells, demonstrating high application potential in real samples.

As an important biomarker, thrombin (TB) is a major player in thrombosis and hemostasis and has attracted increasing attention involving its determination. Herein a universal and ultrasensitive fluorescence biosensor based on a binding-induced 3D-bipedal DNA walker and catalytic hairpin assembly (CHA) strategy has been proposed for cascade signal amplification detection of thrombin. In this study, we designed two proximity probes (foot 1 and foot 2) which include a specific affinity ligand for TB binding and a Pb2+-dependent DNAzyme tail sequence. In the presence of TB, the simultaneous binding of TB to foot 1 (F1) and foot 2 (F2) via TB aptamer (TBA) brings the tail sequences into close proximity and the melting temperature for tail sequences and track DNA is increased, allowing the Pb2+-dependent DNAzyme to cleave the track DNA into two short fragments which have lower affinities for the DNAzyme and, finally, leading to the release of trigger DNA (T-DNA) for subsequent CHA reaction. In the meantime, the dissociated DNA walkers (F1 and F2) explore adjacent unwound track DNA, and the walking procedure is conducted. Unlike the conventional unipedal DNA walkers that anchor foot DNA and track DNA on the same sensing surface, the proposed 3D-bipedal DNA walking machine can not only increase the local concentration of track DNA but can also improve the walking efficiency and expand the range of the walkers to some extent due to the two free feet. Moreover, with the advantages of superior sensitivity and excellent specificity, this biosensing platform exhibits a huge potential in practical application in biomedical research and clinical diagnosis.