Carbon dots combined with masking agent for high selectivity detection of Cr(VI) to overcome interference associated challenges.

Hexavalent chromium (Cr(VI)) determination is of great importance to the public health because of its extensive sources and high toxicity. However, interference from non-target ions and complex matrix remains challenges for Cr(VI) detection. In this work, we constructed a novel sensing system for high selectivity detection of Cr(VI), which is composed of strong emitting carbon dots (CE-CDs) and a specific masking agent. The detection conditions, anti-interference capability and the sensing and masking mechanisms of CE-CDs-based sensing method were systematically investigated. The results revealed that the optimal detection conditions included pH 4-10, reaction time 180 s and CE-CDs concentration 18 mg/L. Under optimal conditions, the linear range of the method was up to 500 µm, and the detection limit was as low as 23 nM. In addition, the interference of Hg(II) can be accurately eliminated by using DMPS, an effective masking agent. During the sensing process, inner filter effect and ion-molecular interaction between Cr(VI) and CE-CDs accounted for the fluorescence quenching mechanism, while the efficient masking was attributed to the strong coordination interaction between Hg(II) and DMPS. Most notably, this method had broad applicability, even for the trace detection of Cr(VI) in colored leather with complex matrix. These findings indicate that this approach is expected to open up new avenues for Cr(VI) detection.

A simple and feasible fluorescent approach for rapid detection of hexavalent chromium based on gold nanoclusters.

Hexavalent chromium (Cr6+) owns hypertoxicity, non-biodegradability, and carcinogenicity, thus the detection of Cr6+ is of paramount significance for environmental monitoring and human health maintenance. Herein, a simple, rapid, and feasible fluorescent method based on gold nanoclusters (AuNCs) was established for determination of Cr6+. The AuNCs was coated by a simple and fast one-pot method using d-histidine (d-His) and polylysine (P-Lys) as stabilizers and reductants, which could be quenched by the addition of Cr6+ owing to the aggregation of AuNCs and fluorescence resonance energy transfer (FRET) between AuNCs and Cr6+. Under the optimal conditions, the fluorescent sensor exhibited good linearity within 10-10000 µg/L with limit of detection of 7.2 µg/L. The developed sensor possessed favorable sensitivity and selectivity. Additionally, the proposed method also had favorable recovery with good precision and accuracy within the actual sample, including celery cabbage, rice, capsule shell, and river water.

Colorimetric and fluorescent probes for the rapid detection of profenofos in farmland system.

Colorimetric and fluorescent sensors were developed for the detection of profenofos. The colorimetric assay relied on the aggregation of cysteine modified gold nanoparticles (Au-cys) composite caused by the hydrogen bond and Au-S bond between profenofos and Au-cys. The further addition of S, N-doped carbon quantum dots (CDs) (fluorescence quantum yield up to 98%) into the Au-cys system depended on the change of fluorescence intensity of Au-cys-CDs owing to the inner filter effect between Au-cys and CDs. Under the optimal conditions, the sensor exhibits good linearity within 0.2-1.2 mg L-1 and 20-320 µg L-1, and limit of detection of 21.7 µg L-1 and 5.5 µg L-1 in colorimetry and fluorescence mode, respectively. The developed sensor did not only possess favorable selectivity and sensitivity, but also feasibility of usage in the actual detection of profenofos in farmland system samples.

Glutathione-responsive PLGA nanocomplex for dual delivery of doxorubicin and curcumin to overcome tumor multidrug resistance.

Aim: This work aims to develop an injectable nano-drug delivery system to overcome tumor multidrug resistance (MDR). Methods: A drug delivery nanoplatform based on PEGylated PLGA with glutathione (GSH) responsivity was constructed for dual delivery of doxorubicin and curcumin (termed DCNP), and its MDR reversal efficiency was studied in vitro and in vivo. Results: The DCNPs exhibited a rapid drug release profile under high GSH concentration and could enhance the cellular uptake and cytotoxicity of doxorubicin to MDR cancer cells. Moreover, the DCNPs showed better biocompatibility, longer blood circulation and enhanced antitumor efficiency compared with free drugs. Conclusion: The GSH-responsive nanocarrier is believed to be a promising candidate for overcoming tumor MDR.

A pH-Responsive System Based on Fluorescence Enhanced Gold Nanoparticles for Renal Targeting Drug Delivery and Fibrosis Therapy.

BACKGROUND: Stimuli-responsive gold nano-assemblies have attracted attention as drug delivery systems in the biomedical field. However, there are challenges achieving targeted delivery and controllable drug release for specific diseases. MATERIALS AND METHODS: In this study, a glutathione (GSH)-modified fluorescent gold nanoparticle termed AuLA-GSH was prepared and a Co2+-induced self-assembly drug delivery platform termed AuLA-GSH-Co was constructed. Both the pH-responsive character and drug loading behavior of AuLA-GSH-Co were studied in vitro. Kidney-targeting capability was investigated in vitro and in vivo. Finally, the anti-fibrosis efficiency of AuLA-GSH-Co in a mouse model of unilateral ureteral obstruction (UUO) was explored. RESULTS: AuLA-GSH-Co was sensitive to pH changes and released Co2+ in acidic conditions, allowing it to have controllable drug release abilities. AuLA-GSH-Co was found to improve cellular uptake of Co2+ ions compared to CoCl2 in vitro. AuLA-GSH exhibited specific renal targeting and prolonged renal retention time with low non-specific accumulation in vivo. Moreover, the anti-fibrosis efficiency of AuLA-GSH-Co was higher compared to CoCl2 in a mouse model of unilateral ureteral obstruction (UUO). CONCLUSION: AuLA-GSH-Co could greatly enhance drug delivery efficiency with renal targeting capability and obviously relieve renal fibrosis, providing a promising strategy for renal fibrosis therapy.

Hydrophilic Porous Poly(l-Lactic Acid) Nanomembranes: Self-Assembly, and Anti-Biofouling and Anti-Thrombosis Effects.

Hydrophilic PEGylated porous self-assembled nanomembranes (PSANMs) with average thickness and pore diameter of ca. 10 and 20-24 nm were successfully prepared by an emulsification-induced programmable self-assembly strategy. The hydrophilicity, anti-biofouling, and anti-thrombosis properties of PEGylated PSANMs were largely improved in comparison with the nonfunctionalized PSANMs, which could transform into hydrophilic (PEGylated PSANMs, minimum water contact angle: 38.8°) from hydrophobic units (PSANMs, maximum water contact angle: 137.5°) with increasing PEG density and length. The total protein adsorption of PEGylated PSANMs was about six times lower than that of the PSANMs, while the thrombosis of the PEGylated PSANMs (maximum R-time: 5.37 min) was also greatly relieved in comparison with the PSANMs (minimum R-time: 2.93 min). Such PEG-modified PSANMs may have applications in drug delivery and tissue and organ repair in vivo.

A stimuli-responsive drug release nanoplatform for kidney-specific anti-fibrosis treatment.

The renoprotective effects of hypoxia inducible-factor (HIF) activators have been demonstrated by improving renal hypoxia in chronic kidney disease. Cobalt chloride is one of the most widely used HIF activators in biomedicine; however, poor kidney targeting and undesirable side effects greatly limit its clinical applications. Here, we report a novel stimuli-responsive drug release nanoplatform in which glutathione (GSH)-modified Au nanoparticles (GLAuNPs) and Co2+ self-assemble into nanoassemblies (GLAuNPs-Co) through coordination interactions between empty orbitals of Co2+ and lone pairs of GSH. The GLAuNPs, when used as a drug carrier, demonstrated high drug loading capacity and pH-triggered drug release after assembling with Co2+. The acidic environment of lysosomes in renal fibrosis tissues could disassemble GLAuNPs-Co and release Co2+. Moreover, encapsulation of the Co2+ ions in the GLAuNPs greatly lowered the cytotoxicity of Co2+ in kidney tubule cells. Tissue fluorescence imaging showed that GLAuNPs-Co specifically accumulated in the kidneys, especially in the renal proximal tubules. After GLAuNPs-Co was intraperitoneally injected into ureter-obstructed mice, significant attenuation of interstitial fibrosis was exhibited. The beneficial effects can be mainly ascribed to miR-29c expression restored by HIF-α activation. These findings revealed that GLAuNPs-Co have pH-responsive drug release and renal targeting capabilities; thus, they are a promising drug delivery platform for treating kidney disease.

Small-Sized Cationic miRi-PCNPs Selectively Target the Kidneys for High-Efficiency Antifibrosis Treatment.

Small-sized cationic miRi (microRNA-21 inhibitor)-PCNPs (low molecular weight chitosan (LMWC)-modified polylactide-co-glycoside (PLGA) nanoparticles (PLNPs)) with special kidney-targeting and high-efficiency antifibrosis treatment are fabricated through coupling miRi, PLGA, and LMWC. In the miRi-PCNPs, easily degraded miRi is encapsulated in PCNPs and thus prevented from degradation by nuclease. Cytotoxicity, immunotoxicity, and systemic toxicity assays and in vitro and ex vivo fluorescence imaging suggest that PCNPs possess excellent biocompatibility, higher cellular uptake efficiency, and selective kidney-targeting capacity. Western blotting, pathological staining, and real-time polymerase chain reaction analyses show that the therapeutic effect of miRi-PCNPs on kidney fibrosis is much higher than that of miRi, which is mainly through suppressing transforming growth factor beta-1/drosophila mothers against decapentaplegic protein 3 (TGF-ß1/Smad3) and extracellular signal-regulated kinases/mitogen-activated protein kinase signaling pathway by inhibiting the expression of microRNA-21. For example, the tubule damage index and tubulointerstitial fibrosis area in the miRi-PCNPs group are ≈2.5-fold lower than those in the saline and bare miRi groups. The miRi-PCNPs with special kidney-targeting and high-efficiency antifibrosis treatment may represent a promising strategy for designing and developing a therapeutic treatment for kidney fibrosis.

Coordinatively Self-Assembled Luminescent Gold Nanoparticles: Fluorescence Turn-On System for High-Efficiency Passive Tumor Imaging.

A fluorescence turn-on system for highly efficient and prolonged tumor imaging has been established by a Co2+-induced coordination self-assembly strategy, in which luminescent glutathione (GSH)-modified gold nanoparticles (LGAuNPs) are assembled into LGAuNPs assemblies (LGAuNPs-Co) through a coordination bond between an unoccupied orbit of Co2+ and lone pair electrons of GSH on the surface of LGAuNPs. The LGAuNPs-Co is sensitive to microenvironment pH, and its quenched luminescence will be turned on in tumor tissues (acidic microenvironment), which behaves as a fluorescence turn-on system for passive tumor imaging. The fluorescence turn-on system combines advantages of the enhanced permeability and retention (EPR) effect of NPs and pH-induced fluorescence turn-on property at the tumor site, which results in a larger fluorescence intensity (FI) difference between normal and tumor tissues as compared with that of luminescent Au NPs (LAuNPs, only with the EPR effect) (∼12-fold). Such a large FI difference results in that LGAuNPs-Co has rapid (∼1.6 h), persistent (∼24 h p.i.), and highly efficient tumor targeting capability in comparison with LGAuNPs. Moreover, the LGAuNPs-Co also has much longer tumor retention, faster renal clearance, and lower reticuloendothelial system (RES) uptake than LGAuNPs. Therefore, the fluorescence turn-on system is very promising for cancer diagnosis and therapy.

Highly Stabilized Core-Satellite Gold Nanoassemblies in Vivo: DNA-Directed Self-Assembly, PEG Modification and Cell Imaging.

Au nanoparticles (NPs) have important applications in bioimaging, clinical diagnosis and even therapy due to its water-solubility, easy modification and drug-loaded capability, however, easy aggregation of Au NPs in normal saline and serum greatly limits its applications. In this work, highly stabilized core-satellite Au nanoassemblies (CSAuNAs) were constructed by a hierarchical DNA-directed self-assembly strategy, in which satellite Au NPs number could be effectively tuned through varying the ratios of core-AuNPs-ssDNA and satellite-AuNPs-ssDNAc. It was especially interesting that PEG-functionalized CSAuNAs (PEG-CSAuNAs) could not only bear saline solution but also resist the enzymatic degradation in fetal calf serum. Moreover, cell targeting and imaging indicated that the PEG-CSAuNAs had promising biotargeting and bioimaging capability. Finally, fluorescence imaging in vivo revealed that PEG-CSAuNAs modified with N-acetylation chitosan (CSNA) could be selectively accumulate in the kidneys with satisfactory renal retention capability. Therefore, the highly stabilized PEG-CSAuNAs open a new avenue for its applications in vivo.

Internal-Modified Dithiol DNA-Directed Au Nanoassemblies: Geometrically Controlled Self-Assembly and Quantitative Surface-Enhanced Raman Scattering Properties.

In this work, a hierarchical DNA-directed self-assembly strategy to construct structure-controlled Au nanoassemblies (NAs) has been demonstrated by conjugating Au nanoparticles (NPs) with internal-modified dithiol single-strand DNA (ssDNA) (Au-B-A or A-B-Au-B-A). It is found that the dithiol-ssDNA-modified Au NPs and molecule quantity of thiol-modified ssDNA grafted to Au NPs play critical roles in the assembly of geometrically controlled Au NAs. Through matching Au-DNA self-assembly units, geometrical structures of the Au NAs can be tailored from one-dimensional (1D) to quasi-2D and 2D. Au-B-A conjugates readily give 1D and quasi-2D Au NAs while 2D Au NAs can be formed by A-B-Au-B-A building blocks. Surface-enhanced Raman scattering (SERS) measurements and 3D finite-difference time domain (3D-FDTD) calculation results indicate that the geometrically controllable Au NAs have regular and linearly "hot spots"-number-depended SERS properties. For a certain number of NPs, the number of "hot spots" and accordingly enhancement factor of Au NAs can be quantitatively evaluated, which open a new avenue for quantitative analysis based on SERS technique.