Aqueous Grown Quantum Dots with Robust Near-Infrared Fluorescence for Integrated Traumatic Brain Injury Diagnosis and Surgical Monitoring.

Surgical intervention is the most common first-line treatment for severe traumatic brain injuries (TBIs) associated with high intracranial pressure, while the complexity of these surgical procedures often results in complications. Surgeons often struggle to comprehensively evaluate the TBI status, making it difficult to select the optimal intervention strategy. Here, we introduce a fluorescence imaging-based technology that uses high-quality silver indium selenide-based quantum dots (QDs) for integrated TBI diagnosis and surgical guidance. These engineered, poly(ethylene glycol)-capped QDs emit in the near-infrared region, are resistant to phagocytosis, and importantly, are ultrastable after the epitaxial growth of an aluminum-doped zinc sulfide shell in the aqueous phase that renders the QDs resistant to long-term light irradiation and complex physiological environments. We found that intravenous injection of QDs enabled both the precise diagnosis of TBI in a mouse model and, more importantly, the comprehensive evaluation of the TBI status before, during, and after an operation to distinguish intracranial from superficial hemorrhages, provide real-time monitoring of the secondary hemorrhage, and guide the decision making on the evacuation of intracranial hematomas. This QD-based diagnostic and monitoring system could ultimately complement existing clinical tools for treating TBI, which may help surgeons improve patient outcomes and avoid unnecessary procedures.

[In vivo tumor imaging and therapy based on near-infrared cadmium-free quantum dots].

Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep tissue penetration, shows great potential for tumor imaging in vivo and therapy. Ⅰ-Ⅲ-Ⅵ quantum dots exhibit high brightness, broad excitation, easily tunable emission wavelength and superior stability, and do not contain highly toxic heavy metal elements such as cadmium or lead. These advantages make Ⅰ-Ⅲ-Ⅵ quantum dots attract widespread attention in biomedical field. This review summarizes the recent advances in the controlled synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots and their applications in tumor imaging in vivo and therapy. Firstly, the organic-phase and aqueous-phase synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots as well as the strategies for regulating the near-infrared photoluminescence are briefly introduced; secondly, representative biomedical applications of near-infrared-emitting cadmium-free quantum dots including early diagnosis of tumor, lymphatic imaging, drug delivery, photothermal and photodynamic therapy are emphatically discussed; lastly, perspectives on the future directions of developing quantum dots for biomedical application and the faced challenges are discussed. This paper may provide guidance and reference for further research and clinical translation of cadmium-free quantum dots in tumor diagnosis and treatment.

The role and mechanism of TXNDC5 in disease progression.

Thioredoxin domain containing protein-5 (TXNDC5), also known as endothelial protein-disulfide isomerase (Endo-PDI), is confined to the endoplasmic reticulum through the structural endoplasmic reticulum retention signal (KDEL), is a member of the PDI protein family and is highly expressed in the hypoxic state. TXNDC5 can regulate the rate of disulfide bond formation, isomerization and degradation of target proteins through its function as a protein disulfide isomerase (PDI), thereby altering protein conformation, activity and improving protein stability. Several studies have shown that there is a significant correlation between TXNDC5 gene polymorphisms and genetic susceptibility to inflammatory diseases such as rheumatoid, fibrosis and tumors. In this paper, we detail the expression characteristics of TXNDC5 in a variety of diseases, summarize the mechanisms by which TXNDC5 promotes malignant disease progression, and summarize potential therapeutic strategies to target TXNDC5 for disease treatment.

Building in biologically appropriate multifunctionality in aqueous copper indium selenide-based quantum dots.

Advanced nanoplatforms equipped with different functional moieties for theranostics hold appealing promise for reshaping precision medicine. The reliable construction of an individual nanomaterial with intrinsic near-infrared (NIR) photofunction and magnetic domains is much desired but largely unexplored in a direct aqueous synthesis system. Herein, we develop an aqueous phase synthetic strategy for Mn2+ doping of ZnS shell grown on Zn-Cu-In-Se core quantum dots (ZCISe@ZnS:Mn QDs), providing the optimal NIR fluorescence quantum efficiency of up to 18.9% and meanwhile efficiently introducing paramagnetic domains. The relaxometric properties of the water-soluble Mn-doped QDs make them desirable for both the longitudinal and transverse (T1 and T2) magnetic resonance (MR) contrast enhancement due to the shell lattice-doped Mn2+ ions with slow tumbling rates and favoured spin-proton dipolar interactions with surrounding water molecules. Surprisingly, the incorporation of Mn2+ ions into the shell is found to significantly enhance the production of reactive oxygen species (ROS) by combining both the chemodynamic and photodynamic processes upon NIR light irradiation, showing great potential for efficient photo-assisted ablation of cancer cells. Furthermore, a broad-spectrum excitation range beneficial for bright NIR fluorescence imaging of breast cancer has been proven and offers high flexibility in the choice of incident light sources. Multiparametric MR imaging of the brain has also been successfully demonstrated in vivo.

Bright, Magnetic NIR-II Quantum Dot Probe for Sensitive Dual-Modality Imaging and Intensive Combination Therapy of Cancer.

Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Continuous Flow Synthesis of Persistent Luminescent Chromium-Doped Zinc Gallate Nanoparticles.

Near-infrared persistent luminescent (or afterglow) nanoparticles with the biologically appropriate size are promising materials for background-free imaging applications, while the conventional batch synthesis hardly allows for reproducibility in controlling particle size because of the random variations of reaction parameters. Here, highly efficient chemistry was matched with an automated continuous flow approach for directly synthesizing differently sized ZnGa2O4:Cr3+ (ZGC) nanoparticles exhibiting long persistent luminescence. The key flow factors responsible for regulating the particle formation process, especially the high pressure-temperature and varied residence time, were investigated to be able to tune the particle size from 2 to 6 nm and to improve the persistent luminescence. Upon silica shell encapsulation of the nanoparticles accompanied by an annealing process, the persistent luminescence of the resulting particles was remarkably enhanced. High-fidelity automated flow chemistry demonstrated here offers an alternative for producing ZGC nanoparticles and will be helpful for other compositionally complex metal oxide nanoparticles.

Near-infrared emitting Cu-In-Se/ZnS core/shell quantum dots: aqueous synthesis and sulfur source effects.

The present study reports an aqueous synthesis approach towards Cu-In-Se/ZnS quantum dots with emission in the near-infrared spectral range. The photoluminescence of the dots can be effectively controlled by adjusting the sulfur source, to achieve increased quantum yields (four times higher) and red-shifted emission peaks (from 809 nm to 830 nm).

Ligand-modulated aqueous synthesis of color-tunable copper nanoclusters for the photoluminescent assay of Hg(II).

Water-soluble Cu nanoclusters (NCs) with tunable emission were synthesized through an eco-friendly one-pot aqueous method. Blue-, green-, and red-emitting NCs with the emission peaks at 420 nm, 505 nm, and 630 nm were obtained by employing ethanediamine, cysteine, and glutathione as surface ligands, respectively. The ligand effects on the optical properties of Cu NCs were studied by the single variable method. It has been revealed by systematic characterizations that the dependence of emission color on the structures of ligands was mainly attributed to their different size-tuning effects. Glutathione has the strongest chelating ability and it can significantly reduce the monomer reactivity and thus decrease the supersaturation degree of the reaction, which is favorable for modulating Cu precursor to grow into larger NCs. In contrast, ethanediamine ligand resulted in smaller nanoclusters due to its weaker binding capability. Because of the strong emission and terrific fluorescent stability, Cu NCs capped with ethanediamine, possessing an emission peak at 420 nm when excited at a wavelength of 350 nm, were directly used for probing Hg(II) with satisfying selectivity, presenting a linear range of 0.1-5.0 mM and a detection limit of 33 µM. The sensor showed good performance in real sample analysis with recoveries ranging from 99% to 103%, and comparable accuracy with atomic fluorescence spectroscopy, manifesting the reliability of the current strategy for sensing Hg(II). Graphical abstract Water-soluble copper nanoclusters with blue, green, and red emissions were synthesized by employing ethanediamine, cysteine, and glutathione as surface ligands respectively, and the blue-emitting nanoclusters with strong emission and terrific stability were directly used for selectively sensing Hg2+.

Strongly emitting and long-lived silver indium sulfide quantum dots for bioimaging: Insight into co-ligand effect on enhanced photoluminescence.

Nanoscale ternary chalcogenides have attracted increasing research interest due to their merits of tunable properties and diverse applications in energy and biomedical fields. In this article, silver indium sulfide quantum dots supported by glutathione and polyethyleneimine as dual-ligands have been synthesized through an environmentally friendly and reproducible aqueous method. An emission quantum yield up to 37.2% has been achieved by glutathione as co-ligand bearing electron-rich groups, much higher than that of polyethyleneimine coated quantum dots (4.97%). Both spectroscopic and structural characterizations demonstrate that the photoluminescence enhancement is attributed to change of surface properties by glutathione as co-ligand. Dynamic light scattering (DLS) results and thermogravimetric analysis (TGA) reveal that glutathione covers the QDs with a higher density on the nanocrystal surface than other co-ligands. Therefore, it can effectively passivate the surface trap centers, thus decreasing the non-radiative emission. Moreover, the resultant silver indium sulfide quantum dots present surprisingly long lifetime of 3.69 µs, excellent fluorescent stability and low cytotoxicity, which enables them to be ideal candidate for real-time bioimaging.

One-step electrodeposition of poly(m-aminobenzoic acid) membrane decorated with peptide for antifouling biosensing of Immunoglobulin E.

m-Aminobenzoic acid (ABA) is one popular derivative of highly conductive monomer of aniline, which contains a carboxyl (COOH) group in its skeleton that is beneficial to various bio-interface and bio-analysis. Hence, Poly(m -aminobenzoic acid) (PABA) membrane was firstly electrochemical deposited onto bare electrode surface using a straightforward cyclic voltammetry (CV) method. PABA membrane exhibited excellent electrochemical stability and apparent wrinkle morphology that could effectively enhance response signal and immensely increase specific surface area of electrode. Next, PABA membrane was decorated with well-designed hairpin aptamer and preferred antifouling peptide in sequence to construct a two-layer architectural bio-interface that could present both sensitive target recognition capability and excellent antifouling ability. Benefiting from the electrodeposited PABA membrane to enhance electrochemical response signal, the developed biosensor performed excellent sensitivity toward target protein, meanwhile, associated with good selectivity and reproducibility attributing to the favored peptide that was able to decline nonspecific protein adsorption and improve target recognition.

Biocompatible off-stoichiometric copper indium sulfide quantum dots with tunable near-infrared emission via aqueous based synthesis.

The present study reports an aqueous synthesis approach towards off-stoichiometric copper indium sulfide quantum dots with emissions in the near-infrared spectral range. The photoluminescence properties of the dots, and in particular the appearance of dual emission at high Cu deficiency, were studied with temperature-dependent steady-state and transient photoluminescence spectroscopy.

Antifouling and ultrasensitive biosensing interface based on self-assembled peptide and aptamer on macroporous gold for electrochemical detection of immunoglobulin E in serum.

Accurate detection of protein biomarkers in complex media remains a challenge due to severe nonspecific adsorption and biofouling, and sensing interfaces that combine the high sensitivity and antifouling ability are highly desirable. Herein, an antifouling sensing interface capable of sensitively assaying immunoglobulin E (IgE) in biological samples was constructed. The sensing interface was fabricated through the self-assembly of a zwitterionic peptide and the IgE aptamer onto a macroporous Au substrate, which was electrochemically fabricated with the aid of multilayer polystyrene nanospheres self-assembled on glassy carbon electrode. Due to the huge surface area arising from porous morphology and high specificity of aptamer, the developed electrochemical biosensor exhibits ultrahigh sensitivity and selectivity towards IgE, with the linear range of 0.1-10 pg mL-1, and a very low limit of detection down to 42 fg mL-1. Interestingly, owing to the presence of the zwitterionic peptide, the biosensing interface can satisfyingly reduce the nonspecific adsorption and fouling effect. Consequently, the biosensor was successfully applied to detect IgE in complex biological samples, indicating great promise of this peptide-based sensing interface for antifouling assays. Graphical abstract ᅟ.

Poly(3,4-ethylenedioxythiophene) doped with engineered carbon quantum dots for enhanced amperometric detection of nitrite.

An electrochemical sensor for nitrite was fabricated by modifying a glassy carbon electrode (GCE) with the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) that is doped with carbon quantum dots (CQDs). The negatively charged CQDs were doped into PEDOT via electrodeposition to form a conducting polymer nanocomposite on the GCE. The electrode surface has a flake-like nanostructure and a large specific surface area. The elemental mapping analysis revealed that the CQDs are uniformly distributed across the whole nanocomposite. As a result of the superior catalytic activity of CQDs and the good conductivity of PEDOT, the modified GCE displays excellent electrocatalytic activity towards the oxidation of nitrite, and the oxidation peak current is ten times higher than that of a PEDOT modified GCE without CQDs. Under optimum conditions and at a working voltage of 0.80 V (vs. Ag/AgCl), the sensor has a linear response in the 0.5-1110 µM nitrite concentration range, and an 88 nM limit of detection (at S/N = 3). Three different electrodes prepared under the same experimental conditions were applied for the detection of nitrite, and the RSD was 3.1%. The same sensor was employed to quantify nitrite in three replicate measurements, and the RSD was 2.2%. Graphical abstract Poly(3,4-ethylenedioxythiophene) (PEDOT) was doped with carbon quantum dots and deposited on a glassy carbon electrode to obtain an amperometric sensor for nitrite.

Recent advancements in biocompatible inorganic nanoparticles towards biomedical applications.

Due to their intrinsic physical properties potentially useful for imaging and therapy as well as their highly engineerable surface, biocompatible inorganic nanoparticles offer novel platforms to develop advanced diagnostic and therapeutic agents for improved detection and more efficacious treatment of major diseases. The in vivo application of inorganic nanoparticles was demonstrated more than two decades ago, however it turns out to be very complicated as nanomaterials exhibit much more sophisticated pharmacokinetic properties than conventional drugs. In this review, we first discuss the in vivo behavior of inorganic nanoparticles after systematic administration, including the basic requirements for nanoparticles to be used in vivo, the impact of the particles' physicochemical properties on their pharmacokinetics, and the effects of the protein corona formed across the nano-bio interface. Next, we summarize the state-of-the-art of the preparation of biocompatible inorganic nanoparticles and bioconjugation strategies for obtaining target-specific nanoprobes. Then, the advancements in sensitive tumor imaging towards diagnosis and visualization of the abnormal signatures in the tumor microenvironment, together with recent studies on atherosclerosis imaging are highlighted. Finally, the future challenges and the potential for inorganic nanoparticles to be translated into clinical applications are discussed.

The Yin and Yang of coordinating co-solvents in the size-tuning of Fe3O4 nanocrystals through flow synthesis.

The present study reports a continuous flow synthesis of differently sized Fe3O4 nanocrystals stabilized by oleylamine and oleic acid. Oleylamine and oleic acid are particularly investigated to elucidate their roles in tailoring the size and magnetic properties of the resulting particles potentially useful for magnetic resonance imaging.

Mixed Self-Assembled Aptamer and Newly Designed Zwitterionic Peptide as Antifouling Biosensing Interface for Electrochemical Detection of alpha-Fetoprotein.

A sensitive and low-fouling aptasensor for alpha-fetoprotein (AFP) was developed based on mixed self-assembled aptamers and newly designed zwitterionic peptides, where densely immobilized peptides formed an antifouling layer to resist nonspecific protein adsorption, and sparsely attached aptamers acted as the recognizing layer to achieve target binding. The obtained biosensing interface responded to the target AFP with a strikingly selective and sensitive manner, exhibited excellent protein-resistant performance even in complex human serum solution, and showed promising feasibility for the quantitative analysis of AFP in real human serum samples.

Differently sized magnetic/upconversion luminescent NaGdF4:Yb,Er nanocrystals: flow synthesis and solvent effects.

The present study reports a novel approach for synthesizing differently sized magnetic/upconversion luminescent NaGdF4:Yb,Er nanocrystals through flow chemistry. The solvent effects on the control of particle size were particularly investigated for tailoring the size and physical properties of the resulting particles potentially useful for bioimaging.

Aqueous synthesis of PEGylated copper sulfide nanoparticles for photoacoustic imaging of tumors.

By integrating high imaging sensitivity and high resolution in a single modality, photoacoustic (PA) imaging emerges as a promising diagnostic tool for clinical applications. Benefiting from the absorption in the near-infrared region (NIR), copper sulfide nanoparticles (NPs) as a contrast agent are potentially useful for increasing the sensitivity of PA imaging. However, the aqueous synthesis of size-tunable, biocompatible and colloidally stable copper sulfide NPs remains challenging due to the intrinsic dipole-dipole interactions among particles. In this work, aqueous synthesis of PEGylated copper sulfide NPs with controllable size between 3 and 7 nm was developed. The particle size-dependent contrast enhancement effect of the copper sulfide NPs for PA imaging was carefully studied both in vitro and in vivo. Although the contrast enhancement effect of the copper sulfide NPs is proportional to particle size, the in vivo studies revealed that copper sulfide NPs smaller than 5 nm presented higher tumor imaging performance, especially at the tumor boundary site, which was further discussed in combination with the pharmacokinetic behaviors of differently sized particles.

Insight into strain effects on band alignment shifts, carrier localization and recombination kinetics in CdTe/CdS core/shell quantum dots.

The impact of strain on the optical properties of semiconductor quantum dots (QDs) is fundamentally important while still awaiting detailed investigation. CdTe/CdS core/shell QDs represent a typical strained system due to the substantial lattice mismatch between CdTe and CdS. To probe the strain-related effects, aqueous CdTe/CdS QDs were synthesized by coating different sized CdTe QD cores with CdS shells upon the thermal decomposition of glutathione as a sulfur source under reflux. The shell growth was carefully monitored by both steady-state absorption and fluorescence spectroscopy and transient fluorescence spectroscopy. In combination with structural analysis, the band alignments as a consequence of the strain were modified based on band deformation potential theory. By further taking account of these strain-induced band shifts, the effective mass approximation (EMA) model was modified to simulate the electronic structure, carrier spatial localization, and electron-hole wave function overlap for comparing with experimentally derived results. In particular, the electron/hole eigen energies were predicted for a range of structures with different CdTe core sizes and different CdS shell thicknesses. The overlap of electron and hole wave functions was further simulated to reveal the impact of strain on the electron-hole recombination kinetics as the electron wave function progressively shifts into the CdS shell region while the hole wave function remains heavily localized in CdTe core upon the shell growth. The excellent agreement between the strain-modified EMA model with the experimental data suggests that strain exhibits remarkable effects on the optical properties of mismatched core/shell QDs by altering the electronic structure of the system.

Identification and characterization of an oocyte factor required for sperm decondensation in pig.

Mammalian oocytes possess factors to support fertilization and embryonic development, but knowledge on these oocyte-specific factors is limited. In the current study, we demonstrated that porcine oocytes with the first polar body collected at 33 h of in vitro maturation sustain IVF with higher sperm decondensation and pronuclear formation rates and support in vitro development with higher cleavage and blastocyst rates, compared with those collected at 42 h (P<0.05). Proteomic analysis performed to clarify the mechanisms underlying the differences in developmental competence between oocytes collected at 33 and 42 h led to the identification of 18 differentially expressed proteins, among which protein disulfide isomerase associated 3 (PDIA3) was selected for further study. Inhibition of maternal PDIA3 via antibody injection disrupted sperm decondensation; conversely, overexpression of PDIA3 in oocytes improved sperm decondensation. In addition, sperm decondensation failure in PDIA3 antibody-injected oocytes was rescued by dithiothreitol, a commonly used disulfide bond reducer. Our results collectively report that maternal PDIA3 plays a crucial role in sperm decondensation by reducing protamine disulfide bonds in porcine oocytes, supporting its utility as a potential tool for oocyte selection in assisted reproduction techniques.