Chiral carbon dots derived from tryptophan and threonine for enantioselective sensing of L/D-Lysine.

Presently, most fluorescent probes for amino acid enantiomers detection require metal ions participation, which greatly increases the detection steps and costs, and affects the accuracy of detection results. To solve this problem, a dual pattern recognition sensor of chiral carbon dots (L-Try-Thr-CDs) with a quantum yield of 36.23 % was prepared by a one-step solvothermal method for the highly selective detection of lysine (Lys) enantiomers. Under optimal experimental conditions, the fluorescence and circular dichroism (CD) signals of the obtained L-Try-Thr-CDs could rapidly and effectively responded to L-Lys with limits of detection (LOD) of 16.51 nM and 24.38 nM, respectively, much lower than previously reported sensors. Importantly, the L-Try-Thr-CDs as a dual-mode sensor could not only detect amino acid enantiomers and simplify the steps, but also avoid inaccurate detection results due to unstable metal ions. Furthermore, the L-Try-Thr-CDs could detect L-Lys in living cells via a fluorescence microscope because of their excellent fluorescence characteristics and low toxicity. These results indicated that the dual-mode sensor not only provided a practical strategy for the design of new fluorescent probes, but also possessed outstanding application prospects in the accurate detection of lysine enantiomers.

Combining fluorescent quantum dots with transition metal oxide shell as core-shell nanocomposite for turn-on sensing of ascorbic acid.

Ascorbic acid (AA) is an essential vitamin in humans, and numerous AA detection studies have been conducted. Most quantum dots (QDs)-based approaches depend on redox reactions involving AA, and they require the introduction of an intermediate (e.g., metal ions, OPD, TMB) or the assembly of fluorescent substances with nanosheets (such as MnO2) that can be degraded by AA. These methods are complex, unstable, and are susceptible to interferences. To address these problems, a core-shell fluorescence probe was developed for turn-on sensing of AA. The transition metal oxide shell FeOOH was generated around the surface of CuInZnS QDs to quench the fluorescence. In the presence of AA, the FeOOH shell was decomposed into Fe2+ and the fluorescence of QDs was recovered. Using a physical shell, the obtained nanocomposite realized direct AA detection, avoiding the effects of interfering substances caused by QDs exposure. Moreover, our probe showed great potential in point-of-care tests and was readily adapted for use as a smartphone-assisted paper sensor.

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice.

During spermiogenesis, haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes, which are required for successful fertilization. Severe deformities in flagella cause a male infertility syndrome, multiple morphological abnormalities of the flagella (MMAF), while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential. However, evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited. Here, we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38 (Ccdc38) via inducing a nonsense mutation and find that the males are infertile. The Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF phenotypes. We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm. Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3, a protein associated with acrosome biogenesis, in testes and an aberrant distribution of TEKT3 in sperm. We finally show that intracytoplasmic sperm injection overcomes Ccdc38-related infertility. Our study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

Influence of l-NAME -induced hypertension on spermatogenesis and sperm tsRNA profile in mice.

Sperm is the key media between the father's aberrant exposure and the offspring's phenotype. Whether paternal hypertension affects offspring through sperm epigenetics remains to be explored. To investigate the underlying mechanisms, we constructed a hypertensive mice model induced by drinking l-NAME and found that spermatocytes and spermatids in the testis were increased significantly after l-NAME treatment. The sequencing of sperm showed that tsRNA profiles changed with 315 tsRNAs (195 up-regulated and 120 down-regulated) altered. Meanwhile, KEGG pathway analysis showed that the target genes of these altered tsRNAs were involved in influencing some important signaling pathways, such as the cAMP signaling path, the mTOR signaling path, the Hippo signaling path, and the Ras signaling path. Bioinformatics of tsRNA-miRNA-mRNA pathway interactions revealed several ceRNA mechanisms, such as tsRNA-00051, the ceRNA of miR-128-1-5p, co-targeting Agap1. This study provides evidence for enriching and further understanding the pathophysiology and paternal epigenetic mechanisms of testicular reproduction, as well as contributing to a rethinking of the transgenerational reprogramming mechanisms of paternal exposure in hypertension.

Progress in the research of cuproptosis and possible targets for cancer therapy.

Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment. According to a recently published study in Science, copper death (cuproptosis) occurs when intracellular copper is overloaded, triggering aggregation of lipidated mitochondrial proteins and Fe-S cluster proteins. This intriguing phenomenon is triggered by the instability of copper ions. Understanding the molecular mechanisms behind cuproptosis and its associated genes, as identified by Tsvetkov, including ferredoxin 1, lipoic acid synthase, lipoyltransferase 1, dihydrolipid amide dehydrogenase, dihydrolipoamide transacetylase, pyruvate dehydrogenase α1, pyruvate dehydrogenase ß, metallothionein, glutaminase, and cyclin-dependent kinase inhibitor 2A, may open new avenues for cancer therapy. Here, we provide a new understanding of the role of copper death and related genes in cancer.

A double rare earth doped CD nanoplatform for nanocatalytic/starving-like synergistic therapy with GSH-depletion and enhanced reactive oxygen species generation.

Cancer has been one of the principal diseases threatening human health in the world. Traditional chemotherapy, radiotherapy and surgery in clinical applications have some disadvantages, such as inefficiency, low specificity, and serious side effects. Therefore, some emerging synergistic therapies have been developed for more accurate diagnosis and more efficient treatment of cancer. Herein, novel Ce-Gd@CDs-GOx nanozymes were obtained by combining magnetic resonance/fluorescence (MR/FL) imaging and nanocatalytic/starving-like synergistic therapy for tumor tissue imaging and efficient cancer treatment. The as-prepared Ce-Gd@CDs-GOx nanozymes with a diameter of 25.0 ± 0.8 nm exhibited favorable physiological stability, negligible toxicity, bright fluorescence and strong T1-weighted MR imaging (MRI) performance (10.97 mM-1 s-1). Moreover, the nanozymes could not only cut off the nutrient supply of tumor cells, but also generate ROS to synergistically enhance antitumor efficacy. The coexistence of Ce3+/Ce4+ in Ce-Gd@CDs-GOx endowed them with attractive capacity for alleviating hypoxia and enhancing GSH consumption to induce the apoptosis of tumor cells. Furthermore, most of the 4T1 cells treated with Ce-Gd@CDs-GOx nanozymes were damaged in the CCK-8 and Calcein-AM/PI staining assays, indicating the excellent efficiency of intracellular synergistic therapy. In summary, this study offered a promising strategy to design a nanoplatform for MR/FL imaging-guided nanocatalytic and starvation-like synergistic therapy of cancer.

LC-MS/MS-Based Absolute Quantitation of Hemoglobin Subunits from Dried Blood Spots Reveals Novel Biomarkers for α-Thalassemia Silent Carriers.

Identification of α-thalassemia silent carriers is challenging with conventional phenotype-based screening methods. A liquid chromatography tandem mass spectrometry (LC-MS/MS)-based approach may offer novel biomarkers to address this conundrum. In this study, we collected dried blood spot samples from individuals with three α-thalassemia subtypes for biomarker discovery and validation. We observed differential expression patterns of hemoglobin subunits among various α-thalassemia subtypes and normal controls through proteomic profiling of 51 samples in the discovery phase. Then, we developed and optimized a multiple reaction monitoring (MRM) assay to measure all detectable hemoglobin subunits. The validation phase was conducted in a cohort of 462 samples. Among the measured hemoglobin subunits, subunit µ was significantly upregulated in all the α-thalassemia groups with distinct fold changes. The hemoglobin subunit µ exhibits great potential as a novel biomarker for α-thalassemia, especially for silent α-thalassemia. We constructed predictive models based on the concentrations of hemoglobin subunits and their ratios to classify the various subtypes of α-thalassemia. In the binary classification problems of silent α-thalassemia vs normal, non-deletional α-thalassemia vs normal, and deletional α-thalassemia vs normal, the best performance of the models achieved average ROCAUCs of 0.9505, 0.9430, and 0.9976 in the cross-validation, respectively. In the multiclass model, the best performance achieved an average ROCAUC of 0.9290 in cross-validation. The performance of our MRM assay and models demonstrated that the hemoglobin subunit µ would play a vital role in screening silent α-thalassemia in clinical practice.

Nitrogen-doped graphene quantum dot-based portable fluorescent sensors for the sensitive detection of Fe3+ and ATP with logic gate operation.

Adenosine triphosphate (ATP) and Fe3+ are important "signaling molecules" in living organisms, and their abnormal concentrations can be used for the early diagnosis of degenerative diseases. Therefore, the development of a sensitive and accurate fluorescent sensor is essential for detecting these signaling molecules in biological matrices. Herein, nitrogen-doped graphene quantum dots (N-GQDs) with cyan fluorescence emission were prepared by thermal cleavage of graphene oxide (GO) with N,N-dimethylformamide (DMF) as a solvent. The synergistic effect of static quenching and internal filtration enabled the selective quenching of N-GQD fluorescence by Fe3+. With the introduction of ATP, Fe3+ in the N-GQDs-Fe3+ system formed a more stable complex with ATP via the Fe-O-P bond, thus restoring the fluorescence of the N-GQDs. Fe3+ and ATP were detected in the linear ranges of 0-34 µM and 0-10 µM with the limits of detection (LOD) of 2.38 nM and 1.16 nM, respectively. In addition to monitoring Fe3+ and ATP in mouse serum and urine, the proposed method was also successfully applied for cytoplasmic imaging of 4T1 cells and in vivo imaging of freshwater shrimps. Moreover, the fluorescence and solution color change-based "AND" logic gate was successfully demonstrated in the biological matrix. Importantly, a complete sensing system was constructed by combining the N-GQDs with hydrogel kits and fluorescent flexible films. Thus, the prepared N-GQDs can be expected to serve as a valuable analytical tool for monitoring Fe3+ and ATP concentrations in biological matrices.

Evaluation of model-based bioequivalence approach for single sample pharmacokinetic studies.

In a traditional pharmacokinetic (PK) bioequivalence (BE) study, a two-way crossover study is conducted, PK parameters (namely the area under the time-concentration curve [AUC] and the maximal concentration [ C max ]) are obtained by noncompartmental analysis (NCA), and the BE analysis is performed using the two one-sided test (TOST) method. For ophthalmic drugs, however, only one sample of aqueous humor, in one eye, per eye can be obtained in each patient, which precludes the traditional BE analysis. To circumvent this issue, the U.S. Food and Drug Administration (FDA) has proposed an approach coupling NCA with either parametric or nonparametric bootstrap (NCA bootstrap). The model-based TOST (MB-TOST) has previously been proposed and evaluated successfully for various settings of sparse PK BE studies. In this paper, we evaluate, via simulations, MB-TOST in the specific setting of single sample PK BE study and compare its performance to NCA bootstrap. We performed BE study simulations using a published PK model and parameter values and evaluated multiple scenarios, including study design (parallel or crossover), sampling times (5 or 10 spread across the dosing interval), and geometric mean ratio (of 0.8, 0.9, 1, and 1.25). Using the simulated structural PK model, MB-TOST performed similarly to NCA bootstrap for AUC. For C max , the latter tended to be conservative and less powerful. Our research suggests that MB-TOST may be considered as an alternative BE approach for single sample PK studies, provided that the PK model is correctly specified and the test drug has the same structural model as the reference drug.

Facile synthesis of nitrogen-doped carbon dots as sensitive fluorescence probes for selective recognition of cinnamaldehyde and l-Arginine/l-Lysine in living cells.

The disorder of amino acid metabolism and the abuse of small molecule drugs pose serious threats to public health. However, due to the limitations of existing detection technologies in sensing cinnamaldehyde (CAL) and l-Arginine/l-Lysine (l-Arg/l-Lys), there is an urgent need to develop new sensing strategies to meet the severe challenges currently facing. Herein, nitrogen-doped carbon dots (N-CDs) were developed using a simple one-pot hydrothermal carbonization method. These N-CDs exhibited numerous distinctive characteristics such as excellent photoluminescence, high water dispersibility, favorable biocompatibility, and superior chemical inertness. Strikingly, the as-prepared CDs as a highly efficient fluorescent probe possessed significant sensitivity and selectivity toward CAL and l-Arg/l-Lys over other analytes with a low detection limit of 58 nM and 16 nM/18 nM, respectively. The fluorescence of N-CDs could be quenched by CAL through an electron transfer process. Then, the strong electrostatic interaction between l-Arg/l-Lys and N-CDs induced the efficient fluorescence recovery. More importantly, the outstanding biosafety and excellent analyte-responsive fluorescence characteristics of N-CDs have also been verified in living cells as well as in serum and urine. Overall, the N-CDs had a wide application prospect in the diagnosis of amino acid metabolic diseases and small molecule drug sensing.

Ionic liquid-based carbon dots as highly biocompatible and sensitive fluorescent probe for the determination of vitamin P in fruit samples.

Vitamin P (VP) known as rutin is one of the common flavonoids, which widely exists in fruits and vegetables and often used as a dietary additive. The rapid and accurate detection of VP in food matrices is critical for evaluating food quality and guiding diet. Herein, a rapid, accurate, and selective detection scheme for VP in fruit samples was proposed for the first time using ionic liquid-based carbon dots (IL-CDs). The synthesized IL-CDs exhibited great biocompatibility and excellent optical properties including high fluorescence intensity, high quantum yield, and good fluorescence stability. Through an internal filtering effect (IFE), VP could greatly reduce the fluorescence of these CDs. In the present study, this probe demonstrated good sensitivity and excellent selectivity toward VP with a low detection limit of 60.0 nmol/L. Moreover, this approach was effectively applied to detect VP in food samples with a recovery range of 97 % to 119 %. More interestingly, the results of cell imaging suggested that IL-CDs were expected to be promising material for bioimaging.

Gadolinium (III) doped carbon dots as dual-mode sensor for the recognition of dopamine hydrochloride and glutamate enantiomers with logic gate operation.

Dopamine hydrochloride (DH) and D-Glutamic acid (D-Glu) are important excitatory neurotransmitters, which are closely relative to central nervous system diseases. Therefore, it is critical to develop the sensitive and facile sensor to precisely monitor the changes of these neurotransmitters. Herein, the gadolinium-doped carbon dots (Gd-CDs) were synthesized by a low-cost and effortless one-pot solvothermal method. These CDs exhibited rapid and reliable fluorescent and colorimetric response signals towards DH and D-Glu. Interestingly, the fluorescence of Gd-CDs could be selectively quenched by DH owing to the fact that the Gd-CDs could coordinate with phenolic hydroxyl groups of DH. Moreover, the quench process was effectively inhibited because the D-Glu competitively coordinated with Gd-CDs-DH system to form a more stable complex. In fluorescence mode, the designed fluorescence sensor possessed an excellent linear relationship for DH in the range from 1 to 10 µM with a low detection limit of 1.26 nM, and the fluorescence could be selectively recovered by D-Glu. In colorimetric manner, DH and D-Glu could be detected by UV-Vis absorption spectrum in the range of 1-15 µM and 1-1.50 mM, respectively. Moreover, the proposed method could not only easily monitor the DH and D-Glu in aqueous solutions as well as mouse serum and human urine samples, but also be employed for detecting DH and D-Glu in cells. Fortunately, the fluorescent and colorimetric dual readout AND logic operation was successfully demonstrated in all-aqueous media. Accordingly, the prepared Gd-CDs hold the potential to become a promising nano-sensor for DH and D-Glu sensing in disease diagnosis areas.

Quantification of human embryonic ζ-globin chains in Southeast Asian deletion (--SEA) carriers.

AIMS: Reactivation of embryonic ζ-globin is a promising strategy for genetic treatment of α-thalassaemia. However, quantification of ζ-globin as a quantitative trait in α-thalassaemia carriers and patients remains incompletely understood. In this study, we aimed to set up a reliable approach for the quantification of ζ-globin in α-thalassaemia carriers, followed by a population study to investigate its expression patterns. METHODS: ζ-globin was purified as monomers from cord blood haemolysate of a Hb Bart's fetus, followed by absolute protein quantification, which was then tested by in-house ELISA system and introduced as protein standard. It was then used for large-scale quantification in peripheral blood samples from 6179 individuals. Finally, liquid chromatography-tandem mass spectrometry (LC-MS/MS) introduced as an independent validating approach by measuring ζ-globin expression in a second cohort of 141-SEA/αα carriers. RESULTS: The ELISA system was proved sensitive in distinguishing individuals with varied extent of ζ-globin. Large scale quantitative study of this --SEA/αα carrier cohort indicated the high diversity of ζ-globin expression ranging from 0.00155 g/L to 1.48778 g/L. Significant positive correlation between ELISA and LC-MS/MS (R=0.400, p<0.001) was observed and it is more sensitive in distinguishing the samples with extreme expression of ζ-globin (R=0.650, p<0.001). CONCLUSION: Our study has reported reliable approaches for the quantification of ζ-globin and presented the expression patterns of ζ-globin among the --SEA/αα carrier population, which might lay a foundation on subsequent genotype-phenotype studies on mechanisms of delayed haemoglobin switch in α-thalassaemia.

Impact of model misspecification on model-based tests in PK studies with parallel design: real case and simulation studies.

This article evaluates the performance of pharmacokinetic (PK) equivalence testing between two formulations of a drug through the Two-One Sided Tests (TOST) by a model-based approach (MB-TOST), as an alternative to the classical non-compartmental approach (NCA-TOST), for a sparse design with a few time points per subject. We focused on the impact of model misspecification and the relevance of model selection for the reference data. We first analysed PK data from phase I studies of gantenerumab, a monoclonal antibody for the treatment of Alzheimer's disease. Using the original rich sample data, we compared MB-TOST to NCA-TOST for validation. Then, the analysis was repeated on a sparse subset of the original data with MB-TOST. This analysis inspired a simulation study with rich and sparse designs. With rich designs, we compared NCA-TOST and MB-TOST in terms of type I error and study power. With both designs, we explored the impact of misspecifying the model on the performance of MB-TOST and adding a model selection step. Using the observed data, the results of both approaches were in general concordance. MB-TOST results were robust with sparse designs when the underlying PK structural model was correctly specified. Using the simulated data with a rich design, the type I error of NCA-TOST was close to the nominal level. When using the simulated model, the type I error of MB-TOST was controlled on rich and sparse designs, but using a misspecified model led to inflated type I errors. Adding a model selection step on the reference data reduced the inflation. MB-TOST appears as a robust alternative to NCA-TOST, provided that the PK model is correctly specified and the test drug has the same PK structural model as the reference drug.

Surface state dominated and carbon core coordinated red-emitting carbon dots for the detection of Cr2O72- and cell imaging.

Cr(VI) as a toxic heavy metal ion can easily enter into the body through drinking or eating and cause liver and kidney diseases as well as cancer. Considering its high biological toxicity and adverse effects on human body, it is desirable to develop a probe to monitor its level in the environment. Herein, a high-efficiency fluorescent nanoprobe based on red emissive carbon dots (R-CDs) was established through a convenient solvothermal strategy. The as-prepared CDs with excitation-independency had the fixed emission wavelength at 627 nm when the excitation wavelength was 560 nm. Further study manifested that the new surface state formed by nitrogen and sulfur doping and the increased conjugated system established through dehydration and carbonization were the main reasons for the fluorescence redshift. In this system, these R-CDs as a fluorescent probe exhibited high specificity and sensitivity to Cr2O72- with the linear range of 4-40 µΜ and the limit of detection could reach 80.00 nM. The quenching of these CDs by Cr2O72- was efficiently induced through a static quenching process. Meanwhile, the obtained CDs could enter into HeLa cells through endocytosis and exhibit bright red fluorescence in cells under a confocal laser scanning microscope. Thus, this work provided a promising probe not only for detecting Cr(VI) in natural environment but also for imaging in cells.

Dual-responsive nano-prodrug micelles for MRI-guided tumor PDT and immune synergistic therapy.

Micelles as nanocarriers not only offer new opportunities for early diagnosis and treatment of malignant cancers but also encounter numerous barriers in the path of efficient delivery of drugs to diseased areas in the body. To address these issues, we developed a pH/GSH responsive nano-prodrug micelle (NLG919/PGA-Cys-PPA@Gd) with a high drug-loading ratio and controlled drug release performance for MRI-guided tumor photodynamic therapy (PDT) and immune synergistic therapy. Under normal conditions, theranostic nanomicelles remained stable and in a photo-quenched state. Upon accumulation in the tumor site, however, the micelles demonstrated tumor microenvironment (TME) triggered photoactive formed-PPA (a photosensitizer) and NLG919 (an indoleamine 2,3-dioxygenase (IDO) inhibitor) release because the amide bonds of PGA-Cys-PPA and the disulfide linkage of Cys were sensitive to pH and GSH, respectively. More importantly, these micelles could avoid the undesired PPA leakage in blood circulation due to the conjugation between PPA and polymers. Furthermore, the obtained micelles could also enhance the contrast of T1-weighted MRI of tumors by virtue of their high relaxivity (r1 = 29.85 mM-1 s-1). In vitro and in vivo results illustrated that the micelles had good biocompatibility and biosafety. On the basis of the efficient drug delivery strategies in PDT and IDO pathway inhibition, this intelligent dual-drug delivery system could serve as an effective approach for MRI guided combination therapy of cancer.

Efficient model-based bioequivalence testing.

The classical approach to analyze pharmacokinetic (PK) data in bioequivalence studies aiming to compare two different formulations is to perform noncompartmental analysis (NCA) followed by two one-sided tests (TOST). In this regard, the PK parameters area under the curve (AUC) and $C_{\max}$ are obtained for both treatment groups and their geometric mean ratios are considered. According to current guidelines by the U.S. Food and Drug Administration and the European Medicines Agency, the formulations are declared to be sufficiently similar if the $90\%$ confidence interval for these ratios falls between $0.8$ and $1.25 $. As NCA is not a reliable approach in case of sparse designs, a model-based alternative has already been proposed for the estimation of $\rm AUC$ and $C_{\max}$ using nonlinear mixed effects models. Here we propose another, more powerful test than the TOST and demonstrate its superiority through a simulation study both for NCA and model-based approaches. For products with high variability on PK parameters, this method appears to have closer type I errors to the conventionally accepted significance level of $0.05$, suggesting its potential use in situations where conventional bioequivalence analysis is not applicable.

Nitrogen-doped carbon dots as a fluorescent probe for folic acid detection and live cell imaging.

The folic acid (FA) level in human body can be used as an indicator for body's normal physiological activities and offer insight into the growth and reproduction of the body's cells. But the abnormal level of FA can cause some diseases. Herein, we designed a simple and convenient approach to prepare fluorescent N-doped carbon dots (N-CDs) for the FA detection. These N-CDs have excellent hydrophilicity, high photostability, and outstanding biocompatibility, as well as excitation-independent emission behavior with typical excitation/emission peaks at 295 nm/412 nm. Upon the existence of FA, the fluorescence emission spectrum of N-CDs was significantly quenched through the synergy of static quenching mechanism and internal filtering effect (IFE). Under optimal conditions, the limit of detection was 28.0 nM (S/N = 3) within the FA concentration range of 0-200.0 µM. In addition, N-CDs were successfully employed to detect FA in real samples such as urine and fetal bovine serum (FBS), with a recovery rate of 99.6%-100.7% for quantitative addition. Furthermore, cell experiments confirmed the low toxicity and the cell imaging performance of these N-CDs, indicating that the obtained N-CDs could be served as a credible quantitative probe for FA analysis in the field of biosensing.

Engineered Exosomes-Based Photothermal Therapy with MRI/CT Imaging Guidance Enhances Anticancer Efficacy through Deep Tumor Nucleus Penetration.

Exosomes, as natural nanovesicles, have become a spotlight in the field of cancer therapy due to their reduced immunogenicity and ability to overcome physiological barriers. However, the tumor targeting ability of exosomes needs to be improved before its actual application. Herein, a multiple targeted engineered exosomes nanoplatform was constructed through rare earth element Gd and Dy-doped and TAT peptide-modified carbon dots (CDs:Gd,Dy-TAT) encapsulated into RGD peptide engineered exosomes (Exo-RGD), which were used to enhance the effect of cancer imaging diagnosis and photothermal therapy. In vitro and in vivo experiments showed that the resulting CDs:Gd,Dy-TAT@Exo-RGD could effectively accumulate at cancer site with an increased concentration owing to the targeting peptides modification and exosomes encapsulation. The tumor therapy effects of mice treated with CDs:Gd,Dy-TAT@Exo-RGD were heightened compared with mice from the CDs:Gd,Dy control group. After intravenous injection of CDs:Gd,Dy-TAT@Exo-RGD into tumor-bearing mice, the temperature of tumors rose to above 50 °C under NIR irradiation and the localized hyperpyrexia induced by CDs could remarkably ablate tumors. The survival rate of the mice was 100% after 60 days. In addition, the CDs:Gd,Dy-TAT@Exo-RGD exhibited higher MRI/CT imaging contrast enhancement of tumor sites than that of CDs:Gd,Dy. Our study identified that engineered exosomes are a powerful tool for encapsulating multiple agents to enhance cancer theranostic efficiency and provide insight into precise personalized nanomedicine.

An "on-off-on" selective fluorescent probe based on nitrogen and sulfur co-doped carbon dots for detecting Cu2+ and GSH in living cells.

The abnormal level of Cu2+ or GSH can cause variety of neurodegenerative diseases in humans. Thus, the selective and sensitive detection of Cu2+ and GSH has inspired intensive research efforts in biological sample analysis fields. Herein, an "on-off-on" fluorescent probe based on nitrogen and sulfur co-doped carbon dots (N,S-CDs) has been successfully prepared for the detection of Cu2+ and GSH. The "turn-off" process of fluorescence in the presence of Cu2+ ions was induced by forming a non-luminescent ground state complex due to the interaction between surface groups of the probe and Cu2+ ions. Moreover, the strong coordination between GSH and Cu2+ could destroy the structure of the complex and restore the fluorescence to "turn-on". This fluorescent probe had excellent selectivity and high sensitivity toward Cu2+ and GSH with the limits of detection (LODs) of 38 nM and 41 nM. More importantly, the as-prepared N,S-CDs served as an efficient fluorescent probe for not only detecting Cu2+ ions in lake water and tap water, and GSH in BSA solution, but also sensing Cu2+ and GSH in living cells. Therefore, these N,S-CDs could be considered as a promising fluorescence probe candidate for environmental monitoring and biological imaging.