Smart DNA nanogel coated polydopamine nanoparticle with high drug loading for chemo-photothermal therapy of cancer.

A smart deoxyribose nucleic acid nanogel coated polydopamine nanosphere hybrid was designed for chemo-photothermal therapy of cancer. The nanohybrid showed good colloid stability, narrow size distribution, high drug loading, good biocompatibility, and high photothermal conversion efficiency, and could release the drug on desired tumor sites.

PDA-PEI-Copolymerized Nanodots with Tailorable Fluorescence Emission and Quenching Properties for the Sensitive Ratiometric Fluorescence Sensing of miRNA in Serum.

Dopamine and polyethyleneimine (PEI) copolymerized nanodots (PDA-PEI nanodots) with both fluorescence emission and quenching features were synthesized by a simple one-step reaction at room temperature. By adjusting the dopamine and PEI ratio as well as the chain length of PEI, the fluorescence emission and quenching properties of PDA-PEI nanodots can be controlled well. Under optimal conditions, the nanodots showed strong green fluorescence emission with an absolute quantum yield of 1-2% and a quenching efficiency of more than 99% to several fluorophores with emission wavelengths ranging from blue to red light regions. The nanodots with a large number of functional groups also showed strong affinity to nucleic acid strands, excellent solubility in aqueous solution, long-term stability, and uniform size distribution. Integrating these attractive features with the specific enzymatic digestion reaction of the DSN enzyme, a highly sensitive ratiometric fluorescence nanoprobe for miRNA analysis was developed. Aminomethylcoumarin acetate (AMCA), which possesses the same excitation wavelength but a well-resolved blue fluorescence emission with PDA-PEI nanodots, was selected as the signal-reporting unit for capture probe labeling, while the inherent green fluorescence of PDA-PEI nanodots served as the reference. According to the ratiometric fluorescence signal, the ratiometric fluorescence nanoprobes showed high sensitivity and good accuracy for the miRNA assay. Because of the high and universal quenching efficiency, stable fluorescence emission, easily assembled interface, and uniform morphology, the nanodots may have great application prospects to serve as a universal nanoplatform for the fabrication of ratiometric fluorescence nanoprobes.

Hyperbranched Tetraphenylethylene Derivatives with Low Non-specific Aggregation-Induced Emission for Fluorescence Recognition of Proteins with Hydrophobic Pockets.

Proteins play an important role in the physiological process of many organisms, and their abnormal level often indicates the occurrence of some diseases. Therefore, protein analysis has important reference value and clinical significance for early diagnosis and therapy of disease. Using human serum albumin (HSA) as a model protein, a series of super-branched tetraphenylethylene (TPE) derivatives with different branching structures and terminal groups are reported herein for highly sensitive and specific recognition of proteins with hydrophobic cages. Benefiting from the hyperbranched structures, these probes showed much higher critical micelle concentrations (CMCs) than most linear TPE-based amphiphilic molecules since the hyperbranched structure not only improved their solubility but also amplified the steric hindrance effect and electrostatic repulsive force to prevent their aggregation. Dynamic light scattering experiments proved that these probes formed dense aggregates at CMC, and such aggregate structures would lead to a higher background fluorescence noise. Hence, a higher CMC is more conducive to the detection of the target with low backgrounds. Among them, P3-COOH with -COOH as the terminal unit and a relatively longer branch showed the highest CMC and the best signal to background ratio (S/N). Mechanism studies showed that P3-COOH was bound to HSA mainly through a hydrophobic force, resulting in a limited P3-COOH molecular movement and less attack from quenchers in solutions, thus leading to greatly enhanced fluorescence intensity. In addition, P3-COOH was also applied to the determination of HSA content in actual human serum samples.

High-Throughput and Real-Time Monitoring of Single-Cell Extracellular pH Based on Polyaniline Microarrays.

Real-time monitoring of extracellular pH (pHe) at the single-cell level is critical for elucidating the mechanisms of disease development and investigating drug effects, with particular importance in cancer cells. However, there are still some challenges for analyzing and measuring pHe due to the strong heterogeneity of cancer cells. Thus, it is necessary to develop a reliable method with good selectivity, reproducibility, and stability for achieving the pHe heterogeneity of cancer cells. In this paper, we report a high-throughput, real-time measuring technique based on polyaniline (PANI) microelectrode arrays for monitoring single-cell pHe. The PANI microelectrode array not only has a high sensitivity (57.22 mV/pH) ranging from pH 6.0 to 7.6 but also exhibits a high reliability (after washing, the PANI film was still smooth, dense, and with a sensitivity of 55.9 mV/pH). Our results demonstrated that the pHe of the cancer cell region is lower than that of the surrounding blank region, and pHe changes of different cancer cells exhibit significant cellular heterogeneity during cellular respiration and drug stimulation processes.

Ratiometric Fluorescence Imaging of Intracellular MicroRNA with NIR-Assisted Signal Amplification by a Ru-SiO2@Polydopamine Nanoplatform.

Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM's green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis.

Hydrazine Hydrate and Dissolved Oxygen-Triggered Near-Infrared Chemiluminescence from CuInS2@ZnS Nanocrystals for Bioassays.

The overwhelming majority of commercially available chemiluminescence (CL) assays are conducted in the eye-visible region. Herein, a near-infrared (NIR) aqueous CL strategy was proposed with CuInS2@ZnS nanocrystals (CIS@ZnS NCs) as emitters. Hydrazine hydrate (N2H4·H2O) could inject electrons into the conduction band of the CIS@ZnS NCs and simultaneously transformed to the intermediate radical N2H3•. N2H3• reduced dissolved oxygen (O2) to O2-•, while the O2-• could inject holes into the valence band of the CIS@ZnS NCs. The recombination of electrons and holes at Cu+ defects in CIS@ZnS NCs eventually yielded efficient NIR CL at around 824.1 nm, which is the longest waveband for NCs CL to the best of our knowledge. The NIR CL could be conveniently performed in the neutral aqueous medium (pH 7.0) with a quantum yield of 0.0155 Einstein/mol and was successfully employed for constructing a signal-off CL biosensor with ascorbic acid as the analyte as well as a signal-on CL biosensor for determining ascorbate oxidase, which indicates that this NIR CL system has a promising potential for bioassays in diverse ways.

Polydopamine with Tailorable Photoelectrochemical Activities for the Highly Sensitive Immunoassay of Tumor Markers.

A simple and highly sensitive photoelectrochemical (PEC) immunoassay sensor was fabricated by using the two forms of polydopamine (PDA), the thin film and nanosphere, to serve as the photoelectrode-modified material and signal reporting label, respectively. The two forms of PDA show similar light absorption behavior but totally different PEC activities. The PDA film can extend the light absorption from the ultraviolet to near infrared light range, transfer a photoelectron to TiO2 nanoparticles and the underlying photoelectrode, and largely amplify the photocurrent response. However, the PDA nanospheres have insignificant photoelectron transport ability. When they are brought close to the PDA film and TiO2 nanocomposite-modified electrode via the sandwich immunoreaction, they function like a black hole to compete with the PDA film for light absorption, resist the access of the electron donor to regenerate the photoactive material, and capture the photoelectron generated from the PDA film. Besides, the heat generated from the PDA nanospheres also contributes to the photocurrent decrease. The PDA nanospheres with multiple quenching effects on the PDA film greatly decrease the photocurrent signal and lead to a highly sensitive PEC immunosensing strategy. Under optimal conditions, a wide linear range from 0.1 to 106 pg·mL-1 is obtained toward carcinoembryonic antigen, with a low limit of detection of 40 fg·mL-1. Besides, the PDA with excellent biosafety can be readily assembled with proteins, which thus simplifies the preparation procedures and decreases the costs. All these features indicate that the whole PDA-based PEC sensing strategy may have great application prospects for the point-of-care assay of various kinds of tumor markers.

Polydopamine nanospheres with multiple quenching effect on TiO2/CdS:Mn for highly sensitive photoelectrochemical assay of tumor markers.

A photoelectrochemical (PEC) immunosensing strategy based on the multiple quenching of polydopamine nanoparticles (PDA NPs) to Mn2+-doped CdS-modified TiO2 nanoparticles (TiO2/CdS:Mn) was designed for the highly sensitive detection of carcinoembryonic antigen (CEA). The uniform PDA NPs possessed good dispersibility, good biocompatibility, and abundant functional groups for biomolecule assembly. They also had unique photophysical properties, with light absorption spanning the visible to infrared light range. When the immune-recognition brought the PDA NPs close to the TiO2/CdS:Mn interface, the PDA NPs competed with TiO2/CdS:Mn to absorb light, consumed photoelectrons generated in the TiO2/CdS:Mn, and hindered the access of electron donors to photoactive materials. The contribution from these aspects thus led to a significant decrease in photocurrent. Benefiting from the multiple quenching mechanism, the PEC immunosensor showed high sensitivity for CEA detection. Under optimal conditions, a low detection limit of 0.02 pg/mL and a wide linear relationship from 0.1 pg/mL to 100 ng/mL were obtained. The immunoassay showed good reproducibility and stability, and good selectivity and high accuracy in serum sample analysis. In this regard, PEC immunosensors may have great application potential for screening tumor markers and the prevention and monitoring of serious diseases.

Ratiometric Detection of DNA and Protein in Serum by a Universal Tripyridinyl RuII Complex-Encapsulated SiO2@Polydopamine Fluorescence Nanoplatform.

Fluorescence ratiometric biosensors are valuable tools for the accurate and sensitive prediction and diagnosis of diseases. However, seldom have fluorescence ratiometric biosensors for protein and DNA been reported because of the shortage of suitable nanoscale scaffolds. Herein, a tripyridinyl RuII complex-encapsulated SiO2@polydopamine (Ru-SiO2@PDA) nanocomposite was designed as a universal platform for fluorescence ratiometric detection of DNA and protein in serum samples. The Ru-SiO2@PDA nanocomposites have a narrow size distribution, exhibit good biosafety, and are convenient for the postmodification of biorecognition elements. Under irradiation, they can emit a stable and strong luminescence at 650 nm and simultaneously quench the fluorescence emitted from the fluorophores getting close to them. Once the capture probes such as single-stranded DNA and aptamer are assembled, the fluorophores labeled on them are then brought close to their PDA shell and quenched. However, the biorecognition behaviors change the probe's configuration and take the fluorophore far away from the PDA shell. Correspondingly, the fluorescence recovers and its ratio to the constant fluorescence reference is linear to the targets' concentration. Using a D-catalyst and thrombin as model analytes, the Ru-SiO2@PDA-based nanoplatform shows high sensitivity and good accuracy in the serum sample analysis. Regarding these attractive properties, the Ru-SiO2@PDA nanoplatform provides a new avenue for the accurate and sensitive fluorescence assay of a wide range of targets in complex systems.

Oxygen defects engineered CdS/Bi2O2.33 direct Z-Scheme heterojunction for highly sensitive photoelectrochemical assay of Hg2.

This work demonstrates that the photoelectrochemical response of the CdS/Bi2O2.33 direct Z-scheme heterojunction, synthesized by in situ deposition of CdS nanocrystals on the defect engineered Bi2O2.33, can be modulated by oxygen defect concentration. The appropriate oxygen defects not only increase the visible light absorption, provide active reaction sites to enhance PEC activity, but also promote the separation of carriers. The formation of CdS/Bi2O2.33 direct Z-scheme heterojunction further improves these properties by extending the visible light absorption and promoting separation and transport of carriers, but avoids the usage of noble metal nanoparticles as electron transfer mediators, thus has a low cost and easy fabrication technology. The CdS/Bi2O2.33 direct Z-scheme junction shows significantly improved photocurrent response as compared with those containing less oxygen defects, and is applied as a photoelectrochemical assay platform for Hg2+. The specific interaction between Hg2+ and the S2- in CdS significantly quenches the photocurrent response of the CdS/Bi2O2.33 due to the formation of HgS. The photocurrent decrease is linear to the concentration of Hg2+ in the range from 10-11 to 10-6 g/mL, with the limit of detection of 3.2 pg/mL. High accuracy and good reproducibility are realized in the real sample analysis of urine, river water, and sea water. The integration of oxygen defect engineering and direct Z-scheme electron transport principle provides a new avenue for fabricating high performance photoelectrochemical materials, which can be further combined with bio-recognition strategy for the ultrasensitive detection of biological molecules.