Photoinduced electron transfer from polymer-templated Ag nanoclusters to G-quadruplex-hemin complexes for the construction of versatile biosensors and logic gate applications.

In this paper, fluorescent Ag nanoclusters (Ag NCs) templated by hyperbranched polyethyleneimine (PEI) are utilized as a versatile probe through the photoinduced electron transfer (PET) between PEI-Ag NCs and G-quadruplex-hemin complexes. In the presence of hemin and target molecule, the specific conjugation with its aptamer induces the conformational change of the DNA sequence, releasing the G-quadruplex sequence part. Once the G-quadruplex-hemin complexes are introduced, electron transfer from the PEI-Ag NCs to G-quadruplex-hemin complexes occurs, resulting in fluorescence quenching. Through changing the sensing DNA sequence, this novel PET system enables the specific detection of target DNA and adenosine triphosphate (ATP) with the wide linear range of 1-200 nM and 5-500 nM, respectively, and the corresponding limit of detection as low as 0.3 nM for target DNA and 1.5 nM for ATP. In addition, the proposed method is successfully applied to the determination of ATP in human serum samples with satisfactory recoveries, and a logic gate is fabricated using target molecules and hemin as inputs and the fluorescence signal of PEI-Ag NCs as an output.

A resonance Rayleigh scattering sensor for sensitive differentiation of telomere DNA length and monitoring special motifs (G-quadruplex and i-motif) based on the Ag nanoclusters and NAND logic gate responding to chemical input signals.

BACKGROUND: Differentiation of telomere length is of vital importance because telomere length is closely related with several deadly diseases such as cancer. Additionally, G-quadruplex and i-motif formation in telomeric DNA have been shown to act as a negative regulator of telomere elongation by telomerase in vivo and are considered as an attractive drug target for cancer chemotherapy. RESULTS: In this assay, Ag nanoclusters templated by hyperbranched polyethyleneimine (PEI-Ag NCs) are designed as a new novel resonance Rayleigh scattering (RRS) probe for sensitive differentiation of telomere length and monitoring special motifs (G-quadruplex and i-motif). In this assay, free PEI-Ag NC probe or DNA sequence alone emits low intensities of RRS, while the formation of PEI-Ag NCs/DNA complexes yields greatly enhanced RRS signals; however, when PEI-Ag NCs react with G-quadruplex or i-motif, the intensities of RRS exhibit slight changes. At the same concentration, the enhancement of RRS signal is directly proportional to the length of telomere, and the sensitivity of 64 bases is the highest with the linear range of 0.3-50 nM (limit of detection 0.12 nM). On the other hand, due to the conversion of telomere DNA molecules among multiple surrounding conditions, a DNA logic gate is developed on the basis of two chemical input signals (K+ and H+) and a change in RRS intensity as the output signal. CONCLUSION: Our results indicate that PEI-Ag NCs can serve as a novel RRS probe to identify DNA length and monitor G-quadruplex/i-motif through the different increasing degrees of RRS intensity. Meanwhile, the novel attributes of the nanoprobe stand superior to those involving dyes or labeled DNA because of no chemical modification, low cost, green, and high efficiency.

Regulating Size and Charge of Liposomes in Microneedles to Enhance Intracellular Drug Delivery Efficiency in Skin for Psoriasis Therapy.

The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug-loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively-charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long-term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)-loaded cationic liposomes-integrated MNs show better therapeutic outcomes than dex-loaded anionic liposomes-integrated MNs in a psoriasis-like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation.

Polyethyleneimine-templated Ag nanoclusters: a new fluorescent and colorimetric platform for sensitive and selective sensing halide ions and high disturbance-tolerant recognitions of iodide and bromide in coexistence with chloride under condition of high ionic strength.

Ag nanoclusters functioned by hyperbranched polyethyleneimine have been developed as a new fluorescent and colorimetric platform for sensitive and selective recognition of halide ions (e.g., Cl(-), Br(-), and I(-)). The recognition mechanism is based on the unique reactions between halide ions and the silver atoms. In particular, halide-induced oxidative etching and aggregation can produce a strong fluorescence quenching of Ag nanoclusters. This sensing system exhibits a remarkably high selectivity toward halide ions over most of anions and cations and shows good linear ranges and lower detection limits: the linear ranges are 0.5-80 µM for Cl(-), 0.1-14 µM for Br(-), and 0.05-6 µM for I(-), respectively; the limits of detection for Cl(-), Br(-), and I(-), at a signal-to-noise ratio of 3, are estimated to be 200, 65, and 40 nM, respectively. Specifically, Br(-) and I(-) could be recognized selectively in the coexistence with Cl(-) under the condition of higher ionic strength, which is a significant advantage in the detection of Br(-) and I(-) in real samples. In addition, the recognition of halide could be performed by the colorimetric method, which is also attractive and promising because of its simplicity, rapidity, reliability, and low cost. Furthermore, this sensing system has been applied successfully to the detection of Cl(-) in real water samples.

Ultrasound-Responsive Polymeric Micelles for Sonoporation-Assisted Site-Specific Therapeutic Action.

Targeting drug delivery remains a challenge in various disease treatment including cancer. The local drug deposit could be greatly enhanced by some external stimuli-responsive systems. Here we develop pluronic P123/F127 polymeric micelles (M) encapsulating curcumin (Cur) that are permeabilized directly by focused ultrasound, in which ultrasound triggers drug release. Tumor preferential accumulation and site-specific sonochemotherapy were then evaluated. Cur-loaded P123/F127 mixed micelles (Cur-M) exhibited longer circulating time and increased cellular uptake compared to free Cur. With the assistance of focused ultrasound treatment, Cur-M showed tumor-targeting deposition in a time-dependent manner following systemic administration. This was due to enhanced permeabilization of tumor regions and increased penetration of Cur-M in irradiated tumor cells by ultrasound sonoporation. Furthermore, Cur-M self-assembly could be regulated by ultrasound irradiation. In vitro Cur release from mixed micelles was greatly dependent on ultrasound intensity but not on duration, suggesting the cavitational threshold was necessary to initiate subsequent sonochemotherapy. In vivo site-specific drug release was demonstrated in dual-tumor models, which showed spatial-temporal release of entrapped drugs following intratumoral injection. The sonoporation-assisted site-specific chemotherapy significantly inhibited tumor growth and the decrease in tumor weight was approximately 6.5-fold more than without exposure to ultrasound irradiation. In conclusion, the established ultrasound-guided nanomedicine targeting deposit and local release may represent a new strategy to improve chemotherapy efficiency.

A tunable pH-sensing system based on Ag nanoclusters capped by hyperbranched polyethyleneimine with different molecular weights.

In this assay, a tunable pH sensing system was developed based on Ag nanoclusters (Ag NCs) capped by hyperbranched polyethyleneimine (PEI) with different molecular weights (abbreviated as Ag NC-PEIs). For instance, when the molecular weight of PEI was 600 or 1800, the fluorescence intensities of Ag NCs exhibited a linear fashion over the pH range 4.10-7.96; when the molecular weight of PEI was 25,000, the pH linear range was from 4.78 to 7.96; when the molecular weight of PEI was 70,000, the pH linear range was 6.09-8.95. According to the molecular weight of PEI 600/1800, 25,000, and 70,000, the color change point was pH 4.10-4.78, 5.33-6.09, and 6.09-6.80, respectively. Therefore, Ag NC-PEI 600 and 1800 were proper to acid conditions; Ag NC-PEI 25,000 was sensitive to weak acid media; while Ag NC-PEI 70,000 was adapted to neutral solution. The tunable and selective color change points brought an excellent feature of Ag NC-PEIs as visual pH indicators, which was flexible and applicable to a variety of environments. Besides, the ratios of absorbance at 415 nm and 268 nm of Ag NCs also showed linear relationships with pH variations. Therefore, there were three ways of this system for sensing pH values, including fluorescence assay, ultraviolet-visible measurement, and visual detection, suggesting that this tunable pH-sensing platform was more feasible, reliable, and accurate.

Polyethylenimine-capped silver nanoclusters as a fluorescence probe for highly sensitive detection of folic acid through a two-step electron-transfer process.

A highly sensitive folic acid (FA) detection method based on the fluorescence quenching of polyethylenimine-capped silver nanoclusters (PEI-AgNCs) was put forward. In the sensing system, FA and PEI-AgNCs were brought into close proximity to each other by electrostatic interaction, and a two-step electron-transfer process, in which the electron was transferred from FA to AgNCs through PEI molecule, led to fluorescence quenching. The fluorescence quenching efficiency of PEI-AgNCs was linearly related to the concentration of FA over the range from 0.1 nM to 2.75 µM. Good linear correlation (R(2) = 0.9981) and a detection limit of 0.032 nM were obtained under optimum conditions. Moreover, the proposed method was used for the determination of FA in real samples with satisfactory results, and those coexistent substances could not cause any significant decrease in the fluorescence intensity of AgNCs. Therefore, the proposed research system is of practical significance and application prospects.

Fluorescent detection of hydrogen peroxide and glucose with polyethyleneimine-templated Cu nanoclusters.

An interesting, simple, and label-free strategy for the detection of hydrogen peroxide and glucose has been developed with polyethyleneimine (PEI)-capped copper nanoclusters as a fluorescence probe in aqueous solution. The PEI-templated Cu nanoclusters which we have synthesized have an average diameter of 1.8 nm and show a blue emission at 480 nm. In the presence of hydrogen peroxide, the fluorescence of the Cu nanoclusters is quenched. Similarly, glucose oxidase catalyzes the oxidation of glucose to gluconic acid and H2O2, so we can also use this probe to detect glucose. Because of the high zymolyte specificity of glucose oxidase, the detection of glucose has good selectivity. Under the optimized experimental conditions, the linear ranges for H2O2 and glucose are 0.5-10 µM and 10-100 µM, respectively. And the detection limits for H2O2 and glucose are 0.4 and 8 µM, respectively. Furthermore, we discussed the mechanism of fluorescence quenching which is caused by the interaction between H2O2 and Cu nanoclusters. This sensing system has been applied successfully to the detection of glucose in human serum samples.

Sensitive signal-on fluorescent sensing for copper ions based on the polyethyleneimine-capped silver nanoclusters-cysteine system.

In this work, we present a label-free sensor for copper ions. This sensor is composed of silver nanoclusters and cysteine. The fluorescence of the silver nanoclusters was quenched by cysteine, which was recovered in the presence of copper ions. This binding of silver nanoclusters to cysteine promoted agglomeration of silver nanoclusters to yield larger non-fluorescent silver nanoparticles. The presence of copper ions resulted in the oxidation of cysteine to form a disulfide compound, leading to recovery of fluorescence of the silver nanoclusters. The fluorescence of the silver nanoclusters in the presence of cysteine increased with increasing concentration of copper ions in the range of 10-200 nM. The detection limit of this sensor for copper ions was 2.3 nM. The silver nanoclusters-cysteine sensor provides a simple, cost-effective, and sensitive platform for the detection of copper ions.