Research Progress on the Strategies for Crossing the Blood-Brain Barrier.

Recently, the incidence of brain diseases, such as central nervous system degenerative diseases, brain tumors, and cerebrovascular diseases, has increased. However, the blood-brain barrier (BBB) limits the effective delivery of drugs to brain disease areas. Therefore, the mainstream direction of new drug development for these diseases is to engineer drugs that can better cross the BBB to exert their effects in the brain. This paper reviews the research progress and application of the main trans-BBB drug delivery strategies (receptor/transporter-mediated BBB crossing, focused ultrasound to open the BBB, adenosine agonist reversible opening of the BBB, aromatic resuscitation, transnasal administration, cell-mediated trans-BBB crossing, and viral vector system-mediated brain drug delivery). Meanwhile, the potential applications, advantages, and disadvantages of these strategies for crossing the BBB are analyzed. Finally, the future development prospects of strategies for crossing the BBB are also discussed. These strategies have potential value for treating brain diseases.

Coaxial dual-path electrochemical biosensing and logic strategy-based detection of lung cancer-derived exosomal PD-L1.

Exosomal programmed death ligand-1 (ExoPD-L1) is a vital marker of immune activation in the early stages of tumor therapy and it can inhibit anti-tumor immune responses. However, due to the low expression of ExoPD-L1 in cancer cells, it is difficult to perform highly sensitive assays and accurately differentiate cancer sources. Therefore, we constructed a coaxial dual-path electrochemical biosensor for highly accurate identification and detection of ExoPD-L1 from lung cancer based on chemical-biological coaxial nanomaterials and nucleic acid molecular signal amplification strategies. The measurements showed that the detected ExoPD-L1 concentrations ranged from 6 × 102 particles per mL to 6 × 108 particles per mL, and the detection limit was 310 particles per mL. Compared to other sensors, the electrochemical biosensor designed in this study has a lower detection limit and a wider detection range. Furthermore, we also successfully identified lung cancer-derived ExoPD-L1 by analyzing multiple protein biomarkers expressed on exosomes through the "AND" logic strategy. This sensor platform is expected to realize highly sensitive detection and accurate analysis of multiple sources of ExoPD-L1 and provide ideas for the clinical detection of ExoPD-L1.

Research progress on nanomaterial-based matrices for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis.

Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a novel soft ionization bio-mass spectrometry technology emerging in the 1980s, which can realize rapid detection of non-volatile, highly polar, and thermally unstable macromolecules. However, the analysis of small molecular compounds has been a major problem for MALDI-TOF MS all the time. In the MALDI analysis process based on traditional matrices, large numbers of interference peaks in the low molecular weight area and "sweet spots" phenomenon are produced, so the detection method needs to be further optimized. The promotion of matrix means the improvement of MALDI performance. In recent years, many new nanomaterial-based matrices have been successfully applied to the analysis of small molecular compounds, which makes MALDI applicable to a wider range of detection and useful in more fields such as pharmacy and environmental science. In this paper, the newly developed MALDI matrix categories in recent years are reviewed initially. Meanwhile, the potential applications, advantages and disadvantages of various matrices are analyzed. Finally, the future development prospects of nanomaterial-based matrices are also prospected.

Combination of microfluidic chips and biosensing for the enrichment of circulating tumor cells.

It has been reported that more than 90% of cancer patients are died from cancer metastasis. Circulating tumor cells (CTCs) could detach from solid tumors to form new lesions via blood transport and play an important role in cancer metastasis and progression. As part of the liquid biopsy, the investigation and analysis toward CTCs are of great importance for prognosis assessment and tumor precision medical treatment. Unfortunately, the enrichment of circulating tumor cells has been a huge challenge due to the fact that CTCs are very rare and vulnerable. Thus, a number of effective strategies have been developed for the enrichment of CTCs. This paper discusses the advantages and disadvantages of label-free and label-based methods commonly used in the isolation of CTCs. In particular, we systematically review the most recent advances in the combination of microfluidic chips and biosensing for the enrichment of circulating tumor cells. Finally, we put forward the current barriers that need to be overcome and developmental trends in the CTCs research.

Plasmonic Enhanced Gold Nanoclusters-Based Photoelectrochemical Biosensor for Sensitive Alkaline Phosphatase Activity Analysis.

Low-toxicity gold nanoclusters-decorated Ag@SiO2 (Au NCs-Ag@SiO2) nanocomposites modified plasmonic photoelectrodes were first fabricated to improve the photoelectric properties of Au NCs and practical application in biological detection. Through adjusting distance between Au NCs and plasmonic silver nanoparticles (Ag NPs), the photocurrent intensity of Au NCs enhanced by 3.8 times attributed to strong competition between enhancement functions of hot electron transfer, local electric field, light scattering effects, and quenching functions of nonradiative energy transfer. Further comparison between experimental results and theoretical simulations were conducted to gain a deeper understanding toward the photoelectric enhancement mechanism. Moreover, Au NCs-Ag@SiO2 nanocomposites was successfully applied to the construction of photoelectrochemical (PEC) biosensors for sensitively detecting alkaline phosphatase activity. This proposed PEC biosensor showed a wide linear range from 0.04 to 400 U·L-1, and a low detection limit of 0.022 U·L-1.

Ratiometric fluorescent nanosensors for ultra-sensitive detection of mercury ions based on AuNCs/MOFs.

Ratiometric fluorescent nanosensors were developed to detect mercury ions (Hg2+) using enhanced dual emissions from glutathione stabilized gold nanoclusters/indium-based metal-organic frameworks modified with cysteine (AuNCs/MIL-68(In)-NH2/Cys). The nanosensors exhibited bright pink fluorescence with AuNCs evenly distributed on MIL-68(In)-NH2. Under 370 nm excitation, the obtained sensor presented double fluorescence emission around 438 nm and 668 nm, which was attributed to MIL-68(In)-NH2 and GSH-AuNCs, respectively. The fluorescence emission was remarkably enhanced after modification with Cys. In the presence of Hg2+, the red fluorescence peak at 668 nm was quenched, while the blue fluorescence peak at 438 nm was slightly altered. The prepared AuNCs/MIL-68(In)-NH2/Cys nanosensors exhibited two linear ranges for the detection of Hg2+, namely from 20 pM to 0.2 µM and 0.2 µM to 60 µM, with a detection limit of 6.7 pM. They also presented high selectivity towards other ions and good performance in real water samples. Moreover, a radial star-shaped microfluidic paper-based analytical device (µPAD), as a straightforward and convenient platform, was successfully fabricated for the visual detection of Hg2+ with a wide detection range from 5 nM to 50 µM.

Reduced graphene oxide/nile blue/gold nanoparticles complex-modified glassy carbon electrode used as a sensitive and label-free aptasensor for ratiometric electrochemical sensing of dopamine.

In this work, glassy carbon electrode (GCE) surface was modified by drop-coating graphene oxide (GO) and nile blue (NB) to form GO/NB/GCE. By using a one-step coreduction treatment under cyclic voltammetry (CV) scanning, gold nanoparticles (AuNPs) were electrodeposited onto GO/NB/GCE surface, simultaneously generating reduced GO (rGO). AuNPs from the prepared rGO/NB/AuNPs/GCE was combined with 5'-SH-terminated aptamer of dopamine (DA) via Au-S coupling to fabricate aptamer-rGO/NB/AuNPs/GCE system. DA specifically combined with its aptamer modified on rGO/NB/AuNPs/GCE surface. CV, electrochemical impedance spectroscopy, square wave voltammetry responses of this system as the working electrode were measured. With the addition of DA, the peak current intensities located at -0.45 V (INB) and 0.15 V (IDA) showed gradually decreased and increased changes, respectively. There was a good linear (R2 = 0.9922) relationship between lg(IDA/INB) and the logarithm of DA concentration (lgCDA) in the CDA range from 10 nM to 0.2 mM, showing a low detection limit of 1 nM. This system as a novel, sensitive and label-free aptasensor was used for ratiometric electrochemical sensing of DA. Experimental results verified that this aptasensor possessed high stability, selectivity and sensitivity towards DA detection, over potential interferents. This aptasensor efficiently determined DA in real biological samples, together with high detection recoveries of 97.0-104.0%.