Textural Precursor Compositions Harvested for Independent Signal Generators: Scaling Micron-Sized Flower-Like Metal-Organic Frameworks as Amplifying Units for Dual-Mode Glycoprotein Assay.

In this work, a micron-sized flower-like metal-organic frameworks (MOFs)-based boronate-affinity sandwich-type immunoassay was fabricated for the dual-mode glycoprotein assay. For proof of concept, the flower-like MOFs were synthesized from transition Cu nodes and tetrakis (4-carboxyphenyl) porphyrin (TCPP) ligands by spontaneous standing assembly. In addition, the specificity toward glycoprotein involved the antigen recognition as well as covalent bonding via the boronate-glycan affinity, and the immediate signal responses were initiated by textural decomposition of the flower-like MOFs. Intriguingly, Cu nodes, of which the valence state is dominant by CuI species, can endow the Fenton-like catalytic reaction of the fluorogenic substrate for generating fluorescence signals. For benefits, TCPP ligands, in which each TCPP molecule has four guest donors, can provide multiple valences for the assembly of cyclodextrin-capped gold nanoparticles via host-guest interaction for colorimetry output. Albeit important, the scaling micrometer patterns for the flower-like MOFs carrying numerous Cu nodes and TCPP ligands can also function as amplifying units, signifying the output signal. The detection limit of the dual-mode glycoprotein assay can reach 10.5 nM for the fluorescence mode and 18.7 nM for the colorimetry mode, respectively. Furthermore, the merits of harvesting different signal generators toward the multimodal readout patterns can allow the mutual verification and make the analytical results more reliable. Collectively, our proposed assay may offer a new idea in combining the inherent textural merits from MOFs for dual signal generators, which can also emphasize accurate detection capability for glycoprotein assay.

The association of circulating lipoprotein lipids and apolipoproteins with risk of endometriosis: a Mendelian randomization study.

BACKGROUND: Endometriosis is a poorly understood disease that affects up to 196 million women worldwide and imposes high costs in terms of economic burden and quality of life of women. Traits of circulating lipids have been related to the onset and progression of endometriosis in previous observational studies but the results have remained contradictory. METHODS: We performed univariable and multivariable Mendelian randomization (MR) analyses using instrument variables to genetically predict the associations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoprotein (apo) A-I and B from the UK Biobank with endometriosis (consisting of 8288 cases and 68 969 controls from the FinnGen consortium). The inverse-variance weighted (IVW) method was used as the primary estimate, whereas MR-Egger and weighted median were conducted as complements to the IVW model. RESULTS: Increased levels of triglycerides were associated with higher risk of endometriosis and endometriosis of the pelvic peritoneum in the univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, triglycerides still retained a robust effect. Decreased levels of apoA-I and HDL cholesterol were associated with increased risk of endometriosis and endometriosis of the pelvic peritoneum in univariable MR analyses. After mutual adjustment, HDL cholesterol retained a robust effect whereas the association for apoA-I was attenuated. CONCLUSIONS: This is the first MR-based evidence to suggest that triglycerides and HDL cholesterol are the predominant traits that account for the aetiological relationship of lipoprotein lipids with risk of endometriosis, in particular endometriosis of the pelvic peritoneum. Further well-designed randomized controlled trials are needed to address these results.

Ethanol Extract of Limonium bicolor Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis by Alleviating Inflammation and Restoring Gut Microbiota Dysbiosis in Mice.

Ulcerative colitis (UC) is a kind of inflammatory bowel condition characterized by inflammation within the mucous membrane, rectal bleeding, diarrhea, and pain experienced in the abdominal region. Existing medications for UC have limited treatment efficacy and primarily focus on symptom relief. Limonium bicolor (LB), an aquatic traditional Chinese medicine (TCM), exerts multi-targeted therapeutic effects with few side effects and is used to treat anemia and hemostasis. Nevertheless, the impact of LB on UC and its mechanism of action remain unclear. Therefore, the objective of this study was to investigate the anti-inflammatory effects and mechanism of action of ethanol extract of LB (LBE) in lipopolysaccharide-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced UC. The results showed that LBE suppressed the secretion of cytokines in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. LBE had protective effects against DSS-induced colitis in mice, decreased the disease activity index (DAI) score, alleviated symptoms, increased colon length, and improved histological characteristics, thus having protective effects against DSS-induced colitis in mice. In addition, it reversed disturbances in the abundance of proteobacteria and probiotics such as Lactobacillus and Blautia in mice with DSS-induced UC. Based on the results of network pharmacology analysis, we identified four main compounds in LBE that are associated with five inflammatory genes (Ptgs2, Plg, Ppar-γ, F2, and Gpr35). These results improve comprehension of the biological activity and functionality of LB and may facilitate the development of LB-based compounds for the treatment of UC.

Multimode Sensing Platform Based on Turn-On Fluorescent Silicon Nanoparticles for Monitoring of Intracellular pH and GSH.

Various physiological activities and metabolic reactions of cells need to be carried out under the corresponding pH environment. Intracellular GSH as an acid tripeptide and an important reducing substance also plays an important role in maintaining cellular acid-base balance and redox balance. Therefore, developing a method to monitor pH and GSH and their changes in cells is necessary. Herein, we developed a novel turn-on fluorescent silicon nanoparticles (SiNPs) using N-(2-aminoethyl)-3-aminopropyltrimethoxysilane as the silicon source and dithiothreitol as the reducing agent via a one-pot hydrothermal method. It was worth mentioning that the fluorescence intensity of the SiNPs increased along with the acidity increase, making the SiNPs have excellent pH and GSH sensing capability. Furthermore, the pH and GSH sensing performance of the SiNPs in the cell was verified by confocal imaging and flow cytometry experiment. Based on the above, the prepared SiNPs had the potential to be used as an intracellular pH and GSH multimode fluorescent sensing platform and exhibited the ability to distinguish between normal cells and cancer cells.

Penidihydrocitrinins A-C: New Polyketides from the Deep-Sea-Derived Penicillium citrinum W17 and Their Anti-Inflammatory and Anti-Osteoporotic Bioactivities.

Three new polyketides (penidihydrocitrinins A-C, 1-3) and fourteen known compounds (4-17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1-17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Additionally, compounds 6, 7, and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 µM, 5.0 µM, and 10 µM.

Hepialiamides A-C: Aminated Fusaric Acid Derivatives and Related Metabolites with Anti-Inflammatory Activity from the Deep-Sea-Derived Fungus Samsoniella hepiali W7.

A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.

Tri-n-butyl phosphate delays tissue repair by dysregulating neutrophil function in zebrafish.

Tri-n-butyl phosphate (TnBP) is a widely used organophosphate ester, but its effects on the regenerative process under damaging circumstances remain unknown. In the present study, zebrafish larvae were exposed to 0, 50, 100, 200 and 1000 µg/L TnBP, and the caudal fins were cut at 72 hours post fertilization (hpf). First, after exposure to TnBP, the number of total neutrophils decreased together with decreased neutrophils in the tail, and TnBP inhibited chemotaxis. Second, reactive oxygen species (ROS) levels in the zebrafish decreased greatly. Following exposure to TnBP, transcription levels of many genes regulating fin regeneration, such as fgf20a, fgfr1a, bmp2a and bmp4, were significantly downregulated, while inflammatory factors such as cxcl8a, cxcl18b, il-6, and tnfa were abnormally upregulated. In addition, TnBP inhibited the regenerative area after caudal fin amputation. The inflammatory state was adverse during the regenerative process. In summary, TnBP exposure is immunotoxic and decreases oxidative stress in injured zebrafish larvae.

High-Performance RuOx Catalyst with Advanced Mesoporous Structure for Oxygen Evolution Reaction.

Polymer electrolyte membrane water electrolysis (PEMWE) is regarded as one of the most important cornerstone technologies in the upcoming hydrogen society. However, one of the major problems it encounters is its slow oxygen evolution kinetics, which necessitates the use of large amounts of precious metal catalysts to ensure a satisfactory reaction rate. Herein, we have prepared a series of RuOx with porous structures and ultrahigh Ru utilization toward the oxygen evolution reaction. All porous samples exhibit an enhanced catalytic performance compared with commercial RuOx. Particularly, for the RuOx-350 sample, the overpotential to reach 10 mA cm-2 is as low as 225 mV. It has obvious advantages among all reported pure RuO2-based catalysts. Here, a new strategy was raised to construct efficient RuO2 electrocatalysts with outstanding activity and stability for water electrolysis technology.

Hydrophilic molecularly imprinted polymers functionalized magnetic carbon nanotubes for selective extraction of cyclic adenosine monophosphate from winter jujube.

In this work, a green strategy was developed to prepare molecularly imprinted polymers functionalized magnetic carbon nanotubes in aqueous phase under mild conditions for cyclic adenosine monophosphate. Thanks to water solubility of chitosan, a natural polysaccharide which is rich in amino and hydroxyl groups, provided the feasibility to synthesize the green molecularly imprinted polymers for water soluble template in aqueous media. Coupled with high-performance liquid chromatography, the method exhibited a short equilibrium time (6 min), high adsorption capacity (22.42 µg/mg), high magnetic susceptibility, and good selectivity to template molecule with the imprinting factor of 2.94. A good linearity in the range of 0.020-3.0 mg/mL for target was obtained with a correlation coefficient of 0.9998. The limit of detection (signal-to-noise ratio = 3) and limit of quantitation (signal-to-noise ratio = 10) of the magnetic solid phase extraction method for cyclic adenosine monophosphate were 5 and 15 ng/mg, respectively. And the practical application of chitosan-based molecularly imprinted polymers as adsorbent to isolate and determine cyclic adenosine monophosphate in real natural samples (winter jujube) was demonstrated.

Molecularly imprinted polymer functionalized magnetic Fe3 O4 for the highly selective extraction of triclosan.

We present a facile strategy to prepare the molecularly imprinted polymers layer on the surface of Fe3 O4 nanoparticles with core-shell structure via sol-gel condensation for recognition and enrichment of triclosan. The Fe3 O4 nanoparticles were first synthesized by a solvothermal method. Then, template triclosan was self-assembled with the functional monomer 3-aminopropyltriethoxysilane on the silica-coated Fe3 O4 nanoparticles in the presence of ethanol and water. Finally, the molecularly imprinted polymers were formed on the surface of silica-coated Fe3 O4 nanoparticles to obtain the product. The morphology, magnetic susceptibility, adsorption, and recognition property of magnetic molecularly imprinted polymers were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffractometry, vibrating sample magnetometry, and re-binding experiments. The magnetic molecularly imprinted polymers showed binding sites with good accessibility, fast adsorption rate, and high adsorption capacity (218.34 µg/g) to triclosan. The selectivity of magnetic molecularly imprinted polymers was evaluated by the rebinding capability of triclosan and two other structural analogues (phenol and p-chlorophenol) in a mixed solution and good selectivity with an imprinting factor of 2.46 was obtained. The application of triclosan removal in environmental samples was demonstrated.

Carbon dots-embedded epitope imprinted polymer for targeted fluorescence imaging of cervical cancer via recognition of epidermal growth factor receptor.

A carbon dots-embedded epitope imprinted polymer (C-MIP) was fabricated for targeted fluorescence imaging of cervical cancer by specifically recognizing the epidermal growth factor receptor (EGFR). The core-shell C-MIP was prepared by a reverse microemulsion polymerization method. This method used silica nanoparticles embedded with carbon dots as carriers, acrylamide as the main functional monomer, and N-terminal nonapeptides of EGFR modified by palmitic acid as templates. A series of characterizations (transmission electron microscope, dynamic light scattering, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, zeta potential, and energy dispersive X-ray spectroscopy) prove the successful synthesis of C-MIP. The fluorescence of C-MIP is quenched by the epitopes of EGFR due to the specific recognition of epitopes of EGFR through their imprinted cavities (analytical excitation/emission wavelengths, 540 nm/610 nm). The linear range of fluorescence quenching is 2.0 to 15.0 µg mL-1 and the determination limit is 0.73 µg mL-1. The targeted imaging capabilities of C-MIP are demonstrated through in vitro and in vivo experiments. The laser confocal imaging results indicate that HeLa cells (over-expression EGFR) incubated with C-MIP show stronger fluorescence than that of MCF-7 cells (low-expression EGFR), revealing that C-MIP can target tumor cells overexpressing EGFR. The results of imaging experiments in tumor-bearing mice exhibit that C-MIP has a better imaging effect than C-NIP, which further proves the targeted imaging ability of C-MIP in vivo. Graphical abstract An oriented epitope imprinted polymer embedded with carbon dots was prepared for the determination of the epitopes of epidermal growth factor receptor and targeted fluorescence imaging of cervical cancer.

Highly Effective Drug Delivery and Cell Imaging Using Fluorescent Double-Imprinted Nanoparticles by Targeting Recognition of the Epitope of Membrane Protein.

Nanocarriers with both targeting ability and stable loading of drugs can more effectively deliver drugs to precise tumor sites for therapeutic effects. Accordingly, we have rationally designed fluorescent molecularly imprinted polymer nanoparticles (FMIPs), which use N-terminal epitope of P32 membrane protein as the primary template and doxorubicin (DOX) as the secondary template. The DOX imprinted cavity can stably carry the drug and the epitope-imprinted cavity allows FMIPs to actively recognize the P32-positive 4T1 cancer cells. The targeted therapeutic effect of DOX-loaded FMIPs (FMIPs@DOX) is investigated in vitro and in vivo. The FMIPs@DOX only causes apoptosis in 4T1 cancer cells compared to C8161 cells (expressing low level of P32). In addition, highly effective inhibition of 4T1 malignant breast tumors using FMIPs@DOX is achieved in the model of tumor-bearing mice. Importantly, the antitumor effect achieved by intravenous injection of FMIPs@DOX is almost identical to that by intratumoral injection. Furthermore, the FMIPs can serve as a targeted fluorescence imaging agent due to the high specificity of the epitope-imprinted cavity and the stable fluorescence of the embedded silicon nanoparticles. These results demonstrate the effectiveness of the FMIPs for active targeted drug delivery and imaging. Furthermore, the FMIPs provide a direction for drug-loaded nanocarrier.

Silicon nanoparticles coated with an epitope-imprinted polymer for fluorometric determination of cytochrome c.

The authors describe a composite consisting of silicon nanoparticles that were first coated with SiO2 and then with a molecularly imprinted polymer (SiNP@SiO2@MIP). The MIP was generated by dual epitope imprinting such that it can recognize cytochrome c (Cyt c). The MIP on the NPs was prepared from the functional monomer zinc(II) acrylate (ZnA), the crosslinker ethylene glycol dimethacrylate and the initiator 2,2'-azoisobutyronitrile. Dual epitope templates for Cyt c included (a) a C-terminal nonapeptide (AYLKKATNE), and (b) an N-terminal nonapeptide (GDVEKGKKI). The chelation between Zn(II) of ZnA and the amino groups or hydroxy groups of the template nonapeptides warrants good recognition and capture of Cyt c. The fluorescence originating from SiNPs has excitation/emission peaks at 360/480 nm and is quenched by Cyt c in the 0.50-40.0 µM concentration range. The correlation coefficient for the calibration plot of the imprinted NPs is 0.9937. The detection limit is 0.32 ± 0.01 µM, the precisions of six replicate detections at levels of 0.5, 20 and 40 µM Cyt c are 3.2, 2.7 and 2.8%, respectively, and the imprinting factor is 2.43. Compared to single epitope template imprinting, dual epitope imprinting results in improved selectivity. The imprinted nanoparticles can discriminate Cyt c even if one amino acid is mismatched. The method was applied to the determination of Cyt c in spiked diluted human serum and gave recoveries between 94.0 and 107.5%. Graphical Abstract A fluorescent material of the architecture silicon nanoparticle@SiO2@molecularly imprinted polymer (SiNP@SiO2@MIP) was fabricated by dual epitope imprinting and a metal-chelating method. The chelation between Zn(II) of the functional monomer zinc(II) acrylate and the amino groups or hydroxy groups of template warrants that the material recognizes and captures cytochrome c well, and this results in fluorescence quenching.

Synthesis of Water-Dispersible Mn2+ Functionalized Silicon Nanoparticles under Room Temperature and Atmospheric Pressure for Fluorescence and Magnetic Resonance Dual-Modality Imaging.

Silicon nanoparticles (Si NPs) have been widely used in fluorescence imaging. However, rigorous synthesis conditions and the single modality imaging limit the further development of Si NPs in the field of biomedical imaging. Here, we reported a method for synthesizing water-dispersible Mn2+ functionalized Si NPs (Mn-Si NPs) under mild experimental conditions for fluorescence and magnetic resonance dual-modality imaging. The whole synthesis process was completed under room temperature and atmospheric pressure, and no special and expensive equipment was required. The synthetic nanoparticles, with favorable pH stability, NaCl stability, photostability, and low toxicity, emitted green fluorescence (512 nm). At the same time, the nanoparticles also demonstrated excellent magnetic resonance imaging ability. In vitro, their T1-weighted magnetic resonance imaging effect was obvious, and the value of longitudinal relaxation degree r1 reached 4.25 mM-1 s-1. On the basis of their good biocompatibility, Mn-Si NPs were successfully used for the fluorescence imaging as well as magnetic resonance imaging in vivo.

Maleic Anhydride Labeling-Based Approach for Quantitative Proteomics and Successive Derivatization of Peptides.

Chemical derivatization is a simple approach for stable-isotope covalent labeling of proteins in quantitative proteomics. Herein we describe the development of a novel maleyl-labeling-based approach for protein quantification. Under optimized conditions, maleic anhydride can serve as a highly efficient reagent to label the amino groups of tryptic peptides. Furthermore, "click chemistry" was successfully applied to obtain the second modification of maleylated peptides via thiol-Michael addition reaction. Accurate quantification was further achieved via the first or/and second step stable-isotope labeling in this study. Our data thus demonstrate that the maleyl-labeling-based method is simple, accurate, and reliable for quantitative proteomics. The developed method not only enables an enhanced sequence coverage of proteins by improving the identification of small and hydrophilic peptides, but also enables a controllable, successive, second derivatization of labeled peptides or proteins, and therefore holds a very promising potential for in-depth analysis of protein structures and dynamics.

Fluorescent Imaging-Guided Chemotherapy-and-Photodynamic Dual Therapy with Nanoscale Porphyrin Metal-Organic Framework.

Imaging-guided therapy systems (IGTSs) are revolutionary techniques used in cancer treatment due to their safety and efficiency. IGTSs should have tunable compositions for bioimaging, a suitable size and shape for biotransfer, sufficient channels and/or pores for drug loading, and intrinsic biocompatibility. Here, a biocompatible nanoscale zirconium-porphyrin metal-organic framework (NPMOF)-based IGTS that is prepared using a microemulsion strategy and carefully tuned reaction conditions is reported. A high content of porphyrin (59.8%) allows the achievement of efficient fluorescent imaging and photodynamic therapy (PDT). The 1D channel of the Kagome topology of NPMOFs provides a 109% doxorubicin loading and pH-response smart release for chemotherapy. The fluorescence guiding of the chemotherapy-and-PDT dual system is confirmed by the concentration of NPMOFs at cancer sites after irradiation with a laser and doxorubicin release, while low toxicity is observed in normal tissues. NPMOFs are established as a promising platform for the early diagnosis of cancer and initial therapy.

One-Pot Microwave Synthesis of Water-Dispersible, High Fluorescence Silicon Nanoparticles and Their Imaging Applications in Vitro and in Vivo.

Silicon nanoparticles (SiNPs) have been reported to be synthesized by microwave-assisted methods under high pressure. However, there is still a lack of knowledge about the synthesis of SiNPs via microwave-assisted methods under normal pressure. Here we developed a new, facile, one-pot microwave-assisted method for the synthesis SiNPs (∼4.2 nm) with excellent water solubility under normal pressure by employing glycerol as the solvent. Furthermore, glycerol might be responsible for the photoluminescence quantum yield (PLQY) value up to 47% for the resultant SiNPs. The use of organic solvent could afford less nanoparticle surface defects compared with those prepared in aqueous solution, thus improving the fluorescent efficiency. The as-prepared SiNPs simultaneously featured bright blue-green fluorescence, long lifetime (∼12.8 ns), obvious up-conversion luminescence originating from two-photon absorption, superbly strong photostability, and favorable low toxicity. As a satisfactory probe, the as-synthesized SiNPs were successfully applied in fluorescence imaging of human cervical carcinoma cell lines (HeLa) and zebrafish.

Development of a DNA-Templated Peptide Probe for Photoaffinity Labeling and Enrichment of the Histone Modification Reader Proteins.

Histone post-translational modifications (HPTMs) provide signal platforms to recruit proteins or protein complexes to regulate gene expression. Therefore, the identification of these recruited partners (readers) is essential to understand the underlying regulatory mechanisms. However, it is still a major challenge to profile these partners because their interactions with HPTMs are rather weak and highly dynamic. Herein we report the development of a HPTM dual probe based on DNA-templated technology and a photo-crosslinking method for the identification of HPTM readers. By using the trimethylation of histone H3 lysine 4, we demonstrated that this HPTM dual probe can be successfully utilized for labeling and enrichment of HPTM readers, as well as for the discovery of potential HPTM partners. This study describes the development of a new chemical proteomics tool for profiling HPTM readers and can be adapted for broad biomedical applications.

Carbon quantum dot stabilized gadolinium nanoprobe prepared via a one-pot hydrothermal approach for magnetic resonance and fluorescence dual-modality bioimaging.

Magnetic resonance imaging (MRI) is used extensively for clinical diagnoses. It is critical to design and develop highly efficient MR contrast agents with simple preparation procedure, low toxicity, and high biocompatibility. Here, we report a carbon quantum dots (CQDs)-stabilized gadolinium hybrid nanoprobe (Gd-CQDs) prepared via a one-pot hydrothermal treatment of the mixture of citrate acid, ethanediamine, and GdCl3 at 200 °C for 4 h. In vitro and in vivo tests confirmed their low toxicity and high biocompatibility. Gd-CQDs were observed to have a higher MR response than gadopentetic acid dimeglumine (Gd-DTPA) because of their high Gd content and hydrophilicity. Moreover, the fluorescence of CQDs was remained in Gd-CQDs. The in vivo MR and fluorescence dual-modality imaging of Gd-CQDs was confirmed with zebrafish embryo and mice as models. The modification of Gd-CQDs with arginine-glycine-aspartic acid (RGD) tripeptide provided a high affinity to U87 cancer cells for targeted imaging. Whereas the MR response showed a depth penetration and spatial visualization, fluorescence revealed the fine distribution of Gd-CQDs in tissues because of its high resolution and sensitivity. We found that Gd-CQDs distributed in the tissues in a heterogeneous mode: they entered into the tissue cells but were observed less in the extracellular matrix. The MR and fluorescence dual-modality imaging of Gd-CQDs makes them a potential contrast agent for clinic applications because of their simple preparation procedure, ease of functionalization, high contrast efficiency, low toxicity, and high biocompatibility.

Gd-Al co-doped mesoporous silica nanoparticles loaded with Ru(bpy)3²âº as a dual-modality probe for fluorescence and magnetic resonance imaging.

Mesoporous silica nanoparticles (MSNs) were co-doped with Gd(3+) and Al(3+) and then loaded with Ru(bpy)3(2+) by ion-exchange to prepare Ru/Gd-Al@MSNs. The as-prepared Ru/Gd-Al@MSNs were applied as contrast agents for in vivo fluorescence and magnetic resonance (MR) dual-modality imaging with a mouse as a model. The effects of Al(3+) and MSNs on longitudinal relaxivity (r1) and fluorescence were investigated using a series of Gd-containing silica nanoparticles, including Gd@MSNs, Gd-Al@MSNs, and Ru/Gd-Al@nonporous silica nanoparticles. Co-doping with Al(3+) improved the loading of Gd(3+); the mesoporous structure improved the water exchange rate. The improvement enhanced the MR imaging efficiency of the Ru/Gd-Al@MSN probe. A higher relaxivity (19.2 mM(-1) s(-1)) was observed compared to that from a commercial contrast agent, Gd-diethylene triamine pentaacetic acid (Gd-DTPA). Importantly, the mesoporous structure provided a large specific surface area for the loading of Ru(bpy)3(2+) by a simple ion-exchange procedure. Intense red fluorescence was observed from Ru/Gd-Al@MSN probes. The versatility of Ru/Gd-Al@MSNs for dual-modality imaging was demonstrated using in vivo fluorescence imaging and T1-weighted MR imaging with a mouse model. The nanoparticles are biocompatible and may be attractive for clinical applications.