Multifunctional Nanoprobe Based on Fluorescence Resonance Energy Transfer for Furin Detection and Drug Delivery.

Triple-negative breast cancer is particularly difficult to treat because of its high degree of malignancy and poor prognosis. A fluorescence resonance energy transfer (FRET) nanoplatform plays a very important role in disease diagnosis and treatment due to its unique detection performance. Combining the properties of agglomeration-induced emission fluorophore and FRET pair, a FRET nanoprobe (HMSN/DOX/RVRR/PAMAM/TPE) induced by specific cleavage was designed. First, hollow mesoporous silica nanoparticles (HMSNs) were used as drug carriers to load doxorubicin (DOX). HMSN nanopores were coated with the RVRR peptide. Then, polyamylamine/phenylethane (PAMAM/TPE) was combined in the outermost layer. When Furin cut off the RVRR peptide, DOX was released and adhered to PAMAM/TPE. Finally, the TPE/DOX FRET pair was constituted. The overexpression of Furin in the triple-negative breast cancer cell line (MDA-MB-468 cell) can be quantitatively detected by FRET signal generation, so as to monitor cell physiology. In conclusion, the HMSN/DOX/RVRR/PAMAM/TPE nanoprobes were designed to provide a new idea for the quantitative detection of Furin and drug delivery, which is conducive to the early diagnosis and treatment of triple-negative breast cancer.

The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair.

Elastin-like polypeptides (ELPs) are thermally responsive biopolymers derived from natural elastin. These peptides have a low critical solution temperature phase behavior and can be used to prepare stimuli-responsive biomaterials. Through genetic engineering, biomaterials prepared from ELPs can have unique and customizable properties. By adjusting the amino acid sequence and length of ELPs, nanostructures, such as micelles and nanofibers, can be formed. Correspondingly, ELPs have been used for improving the stability and prolonging drug-release time. Furthermore, ELPs have widespread use in tissue repair due to their biocompatibility and biodegradability. Here, this review summarizes the basic property composition of ELPs and the methods for modulating their phase transition properties, discusses the application of drug delivery system and tissue repair and clarifies the current challenges and future directions of ELPs in applications.

Cobalt and nitrogen co-doped monolithic carbon foam for ultrafast degradation of emerging organic pollutants via peroxymonosulfate activation.

Cobalt-based catalysts are expected as one of the most promising peroxymonosulfate (PMS) activators for the removal of organic pollutants from industrial wastewater. However, the easy agglomeration, difficult separation, and secondary pollution of cobalt ions limit their practical application. In this study, a novel, highly efficient, reusable cobalt and nitrogen co-doped monolithic carbon foam (Co-N-CMF) was utilized to activate PMS for ultrafast pollutant degradation. Co-N-CMF (0.2 g/L) showed ultrafast catalytic kinetics and higher total organic carbon (TOC) removal efficiency. Bisphenol A, ciprofloxacin, 2,4-dichlorophenoxyacetic acid, and 2,4-dichlorophenol could be completely degraded after 2, 4, 5, and 5 min, and the TOC removal efficiencies were 77.4 %, 68.9 %, 72.8 %, and 79.8 %, respectively, corresponding to the above pollution. The sulfate radical (SO4•-) was the main reactive oxygen species in Co-N-CMF/PMS based on electron paramagnetic resonance. The ecological structure-activity relationship program analysis via the quantitative structure activity relationship analysis and phytotoxicity assessment revealed that the Co-N-CMF/PMS system demonstrates good ecological safety and ecological compatibility. The Co-N-CMF catalyst has good catalytic activity and facile recycling, which provides a fine method with excellent PMS activation capacity for 2,4-dichlorophenol elimination from simulated industrial wastewater. This study provides new insights into the development of monolithic catalysts for ultrafast wastewater treatment via PMS activation.

Gold nanoparticles-decorated peptide hydrogel for antifouling electrochemical dopamine determination.

A reliable and brief ultralow fouling electrochemical sensing system capable of monitoring targets in complex biological media was constructed and validated based on gold nanoparticles-peptide hydrogel-modified screen-printed electrode. The self-assembled zwitterionic peptide hydrogel was prepared by a newly designed peptide sequence of Phe-Phe-Cys-Cys-(Glu-Lys)3 with the N-terminal modified with a fluorene methoxycarbonyl group. The thiol groups on cysteine of the designed peptide are able to self-assemble with AuNPs to form a three-dimensional nanonetwork structure, which showed satisfactory antifouling capability in complex biological media (human serum). The developed gold nanoparticles-peptide hydrogel-based electrochemical sensing platform displayed notably sensing properties for dopamine determination, with a wide linear range (from 0.2 nM to 1.9 µM), a low limit of detection (0.12 nM), and an excellent selectivity. This highly sensitive and ultralow fouling electrochemical sensor was fabricated via simple preparation with concise components that avoid the accumulation of layers with single functional material and complex activation processes. This ultralow fouling and highly sensitive strategy based on the gold nanoparticles-peptide hydrogel with a three-dimensional nanonetwork offers a solution to the current situation of various low-fouling sensing systems facing impaired sensitivity and provides a potential path for the practical application of electrochemical sensors.

Lysosomal escaped protein nanocarriers for nuclear-targeted siRNA delivery.

In the process of drug carrier design, lysosome degradation in cells is often neglected, which makes a considerable number of drugs not play a role. Here, we have constructed a tumor treatment platform (Apn/siRNA/NLS/HA/Apt) with unique lysosomal escape function and excellent cancer treatment effect. Apoferritin (Apn) has attracted more and more attention because of its high uniformity, modifiability, and controllability. Meanwhile, its endogenous nature can avoid the risk of immune response being eliminated. We used aptamer modified iron deficient protein nanocages (Apn) to tightly encapsulate the combination of siRNA and NLS (siRNA/NLS) with influenza virus hemagglutinin (HA peptide). After Apn/siRNA/NLS/HA/Apt was targeted into cells, the acidic environment of lysosome led to the cleavage of Apn nanocages, and the release of siRNA/NLS and HA peptide. HA peptide can destroy lysosome membrane, make siRNA/NLS escape lysosome, and enter the nucleus under the action of NLS, resulting in efficient gene silencing effect. This kind of cancer treatment strategy based on Apn nanocage shows high biocompatibility and unique lysosome escape property, which significantly improves the drug delivery and treatment efficiency. Lysosomal escape protein nanocarriers for nuclear-targeted siRNA delivery.

Activated Plasmonic Nanoaggregates for Dark-Field in Situ Imaging for HER2 Protein Imaging on Cell Surfaces.

Dark-field microscopy (DFM) based on localized surface plasmon resonance (LSPR) was used for observation of experimental phenomena, which is a hopeful nondamaging and non-photobleaching biological imaging technique. In this strategy, plasma nanoaggregates with stronger scattering efficiency were formed in the presence of the target, causing a "turn-on" phenomenon, when asymmetry modified AuNPs were introduced as probes with zero LSPR background. First, Au1-N3 probe and Au2-C≡C probe were designed for the cycloaddition between azide and alkyne to form AuNP dimers under catalytic action by Cu+, which was obtained from the reduction of Cu2+ by sodium ascorbate. The two kinds of probes were successfully used for the detection of Cu2+ in rat serum. Then, to apply this concept to protein on cells, DNA and antibody were modified on the probes. DNA1/Au1-N3 probe and anti-HER2/Au2-C≡C probe were proposed for HER2 protein DFM on cells. By designing an aptamer sequence in primer, the rolling circle amplification (RCA) was introduced in HER2 DFM on cells, and the image signal was much brighter than that from no-RCA. The unique design made it easier to discriminate the target signal from background noise in cell DFM. This method might be used in the fields of molecular diagnostics and cell imaging.

An aggregation-induced emission fluorogen/DNA probe carrying an endosome escaping pass for tracking reduced thiol compounds in cells.

The fluorescent nanoprobes for reduced thiol compounds (represented by glutathione, GSH) are constructed based on the aggregation-induced emission (AIE) luminescence mechanism and endosome escape technology. First, a DNA sequence was designed with the decoration of biotin at the 5'-end, disulfide bound in the internal portion, and amino at the 3'-end. The aptamer of the MCF-7 cell was also one of the most important structures in our DNA sequence for the selectivity of MCF-7 cells. We modified streptavidin-modified magnetic beads (MB) with biotin-modified influenza virus hemagglutinin peptide (HA) and biotin-DNA-amino to form MB/DNA/HA. Carboxyl-modified tetraphenylethylene (TPE), an iconic AIE fluorogen, was bonded with amino-modified DNA by covalent interactions (TPE/DNA). Then, the TPE molecule was attached on the outer layer of MB via biotin-modified TPE/DNA to form MB/DNA/HA/TPE. Compared with traditional AIE/biomolecule conjugates, the nanoprobe had an enhanced endosome escape function, due to the assembly of HA. This construction made the intracellular fluorescence response more accurate. In the presence of reduced thiol compounds (take GSH, for example), the disulfide bond on the DNA was reduced by thiol-disulfide exchange reactions and the TPE molecule was released into the solution. The shedding TPE molecule was more hydrophobic than TPE/DNA and the conversion of TPE/DNA to shedding TPE could lead to the aggregation of the TPE fluorogen. Thus, its fluorescence was enhanced. Under the optimized condition, the fluorescence intensity increased with the increase in concentration of GSH' ranging from 1.0 × 10-9 M to 1.0 × 10-5 M' and the detection limit was 1.0 × 10-9 M. The relative standard deviation (RSD) was calculated to be 3.6%. The recovery in cell homogenate was from 94.5 to 102.7%. The nanoprobe provided a way for the detection of reduced thiol compounds in MCF-7 cells. We envision that, in the near future, our strategy of DNA-instructed AIE could be widely applied for biosensing and bioimaging in vitro and even in vivo with dramatically enhanced sensitivity. Graphical Abstract.

Ligand-modulated aqueous synthesis of color-tunable copper nanoclusters for the photoluminescent assay of Hg(II).

Water-soluble Cu nanoclusters (NCs) with tunable emission were synthesized through an eco-friendly one-pot aqueous method. Blue-, green-, and red-emitting NCs with the emission peaks at 420 nm, 505 nm, and 630 nm were obtained by employing ethanediamine, cysteine, and glutathione as surface ligands, respectively. The ligand effects on the optical properties of Cu NCs were studied by the single variable method. It has been revealed by systematic characterizations that the dependence of emission color on the structures of ligands was mainly attributed to their different size-tuning effects. Glutathione has the strongest chelating ability and it can significantly reduce the monomer reactivity and thus decrease the supersaturation degree of the reaction, which is favorable for modulating Cu precursor to grow into larger NCs. In contrast, ethanediamine ligand resulted in smaller nanoclusters due to its weaker binding capability. Because of the strong emission and terrific fluorescent stability, Cu NCs capped with ethanediamine, possessing an emission peak at 420 nm when excited at a wavelength of 350 nm, were directly used for probing Hg(II) with satisfying selectivity, presenting a linear range of 0.1-5.0 mM and a detection limit of 33 µM. The sensor showed good performance in real sample analysis with recoveries ranging from 99% to 103%, and comparable accuracy with atomic fluorescence spectroscopy, manifesting the reliability of the current strategy for sensing Hg(II). Graphical abstract Water-soluble copper nanoclusters with blue, green, and red emissions were synthesized by employing ethanediamine, cysteine, and glutathione as surface ligands respectively, and the blue-emitting nanoclusters with strong emission and terrific stability were directly used for selectively sensing Hg2+.

Intracellular dark-field imaging of ATP and photothermal therapy using a colorimetric assay based on gold nanoparticle aggregation via tetrazine/trans-cyclooctene cycloaddition.

In this study, we developed a colorimetric ATP assay based on the ATP-induced aggregation of Au nanoparticles (AuNPs). This aggregation modified the local surface plasmon resonance (LSPR) of the AuNPs, which was used to detect and localize ATP in cells via dark-field imaging. The AuNP aggregation process involved the reaction of two types of functionalized AuNPs with each other: tetrazine-modified AuNPs (Au3-N4) and asymmetrically functionalized trans-cyclooctene-modified AuNPs (Au1-(E)-cyclooctene). This cycloaddition reaction occurs without the need for a catalyst such as the Cu ions that are used in the "click" reactions often employed in assays of this type. Initially, we asymmetrically functionalized both types of AuNPs and let them dimerize, which permitted us to explore the resulting wavelength shift in the LSPR of the AuNPs. Then, to facilitate the specific recognition of ATP, a designed DNA (DNA1) containing an ATP aptamer sequence was attached to carboxyl polystyrene microbeads (MBs). After attaching a different DNA (DNA2, which hybridizes with DNA1) to Au1-(E)-cyclooctene, the assay probe MB/DNA1/DNA2/Au1-(E)-cyclooctene (MB/Au1) was generated. While bound to MB/DNA1, the DNA2/Au1-(E)-cyclooctene cannot react with Au3-N4 due to steric hindrance from the MB. However, in the presence of ATP, the probe MB/Au1 dissociates, and the resulting free DNA2/Au1-(E)-cyclooctene can then react with the Au3-N4, leading to the formation of AuNP aggregates. Dark-field microscopy (DFM) images showed that the LSPR of the AuNPs shifted from the green region (AuNP monomers) to the orange-red region (AuNP aggregates) in the presence of intracellular ATP. Moreover, the AuNP aggregates were found to exhibit significant photothermal effects under 808-nm laser irradiation. Upon introducing the probe MB/Au1 and Au3-N4 into HeLa cells in vitro and in vivo, and then irradiating the cells with a 808-nm NIR laser, the resulting AuNP aggregates showed promising photothermal cancer therapy performance. This assay therefore has the potential to be widely used for the identification and determination of nanoparticles in biological DFM and in tumor theranostics. Graphical abstract.

Diagnosis-Therapy Integrative Systems Based on Magnetic RNA Nanoflowers for Co-drug Delivery and Targeted Therapy.

This study was to develop a codrug delivery system for targeting cancer therapy based on magnetic RNA nanoflowers (RNA NF). Compared with traditional nucleic acid structure, convenient separation can be achieved by introducing magnetic nanoparticle (MNP) into RNA NF. Folic acid (FA) modified MNP/RNA NF (FA/MNP/RNA NF) was used as a targeting nanocarrier with excellent biocompatibility to overcome the nonselectivity of MNP/RNA NF. And then, anticancer drug doxorubicin (DOX) and photosensitizer 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) binding with RNA NF were used as codrug cargo models. RNA NF was first used for codrug delivery. So, imaging fluorescent tags, target recognition element, and drug molecules were all assembled together on the surface of MNP/RNA NF. The experimental results suggested that the treatment efficacy of codrug delivery platform (FA/MNP/RNA NF/D/T) was better than single-drug delivery platform (FA/MNP/RNA NF/D). Besides, the FA/MNP/RNA NF was used as a probe for cancer cell detection. The limit of detection was 50 HeLa cells. In conclusion, the codrug delivery platform based on FA/MNP/RNA NF was a promising approach for the intracellular quantification of other biomolecules, as well as a diagnosis-therapy integrative system.

A universal colorimetry for nucleic acids and aptamer-specific ligands detection based on DNA hybridization amplification.

We present a universal amplified-colorimetric for detecting nucleic acid targets or aptamer-specific ligand targets based on gold nanoparticle-DNA (GNP-DNA) hybridization chain reaction (HCR). The universal arrays consisted of capture probe and hairpin DNA-GNP. First, capture probe recognized target specificity and released the initiator sequence. Then dispersed hairpin DNA modified GNPs were cross-linked to form aggregates through HCR events triggered by initiator sequence. As the aggregates accumulate, a significant red-to purple color change can be easily visualized by the naked eye. We used miRNA target sequence (miRNA-203) and aptamer-specific ligand (ATP) as target molecules for this proof-of-concept experiment. Initiator sequence (DNA2) was released from the capture probe (MNP/DNA1/2 conjugates) under the strong competitiveness of miRNA-203. Hairpin DNA (H1 and H2) can be complementary with the help of initiator DNA2 to form GNP-H1/GNP-H2 aggregates. The absorption ratio (A620/A520) values of solutions were a sensitive function of miRNA-203 concentration covering from 1.0 × 10-11 M to 9.0 × 10-10 M, and as low as 1.0 × 10-11 M could be detected. At the same time, the color changed from light wine red to purple and then to light blue have occurred in the solution. For ATP, initiator sequence (5'-end of DNA3) was released from the capture probe (DNA3) under the strong combination of aptamer-ATP. The present colorimetric for specific detection of ATP exhibited good sensitivity and 1.0 × 10-8 M ATP could be detected. The proposed strategy also showed good performances for qualitative analysis and quantitative analysis of intracellular nucleic acids and aptamer-specific ligands.

Graphdiyne-Induced CoN/CoS2 Heterojunction: Boosting Efficiency for Bifunctional Oxygen Electrochemistry in Zinc-Air Batteries.

The performance of zinc-air battery is constrained by the sluggish rate of oxygen electrode reaction, particularly under high current discharge conditions where the kinetic process of the oxygen reduction reaction (ORR) decelerates significantly. To address this challenge, we present a novel phase transition strategy that facilitates the creation of a heteroatom-doped heterointerface (CoN/CoS2). The meticulously engineered CoN/CoS2/NC electrocatalyst displays a superior ORR half-wave potential of 0.87 V and an OER overpotential of 320 mV at 10 mA cm-2. Experimental and computational analysis confirm that the CoN/CoS2 heterostructure optimizes local charge distribution, accelerates electron transfer, and tunes active sites for enhanced catalysis. Notably, this heterojunction improves stability by resisting corrosion and degradation under harsh alkaline conditions, thus demonstrating superior performance and longevity in a custom-made liquid zinc-air battery. This research provides valuable practical and theoretical foundations for designing efficient heterointerfaces in electrocatalysis applications.

Simultaneous electrochemical determination of two analytes based on nuclease-assisted target recycling amplification.

In the present study, a method for simultaneous determination of two different DNAs is developed based on nuclease-assisted target recycling and nanoparticle amplification. The target recycling process is accomplished by taking advantage of the cleavage property of nicking endonuclease (NEase) for specific nucleotide sequences in duplex. In the presence of target DNA, the linker DNA in our detection system can hybridize with the target and be cleaved to form short fragments. Thus the target DNA is released and recognized by another linker DNA, activating the next round of cleavage reaction. On the other hand, two bio-barcode probes, a PbS nanoparticles (NPs)-DNA probe and a CdS NPs-DNA probe, are used for tracing two target DNAs to further amplify the detection signals. Based on a sensitive differential pulse anodic stripping voltammetry (DPASV) method for the simultaneous detection of Pb(2+) and Cd(2+) obtained by dissolving two probes, two different target DNAs are determined with high sensitivity and single-base mismatch selectivity.

Construction of intelligent moving micro/nanomotors and their applications in biosensing and disease treatment.

Micro/nanomotors are containers that pass through liquid media and carry cargo. Because they are tiny, micro/nanomotors exhibit excellent potential for biosensing and disease treatment applications. However, their size also makes overcoming random Brownian forces very challenging for micro/nanomotors moving on targets. Additionally, to achieve desired practical applications, the expensive materials, short lifetimes, poor biocompatibility, complex preparation methods, and side effects of micro/nanomotors must be addressed, and potential adverse effects must be evaluated both in vivo and in practical applications. This has led to the continuous development of key materials for driving micro/nanomotors. In this work, we review the working principles of micro/nanomotors. Metallic and nonmetallic nanocomplexes, enzymes, and living cells are explored as key materials for driving micro/nanomotors. We also consider the effects of exogenous stimulations and endogenous substance conditions on micro/nanomotor motions. The discussion focuses on micro/nanomotor applications in biosensing, treating cancer and gynecological diseases, and assisted fertilization. By addressing micro/nanomotor shortcomings, we propose directions for further developing and applying micro/nanomotors.

The Amplified DNA Logic Gates Based on Aptamer-Receptor Recognition for Cell Detection and Bioimaging.

A powerful and accurate method for identifying and isolating cells would be of great importance due to its sensitivity, gentleness and effectiveness. Here, we designed a receptor-based DNA logic device that allows Boolean logic analysis of multiple cells. For ease of expression, the molecules on the cell surface that can bind to the aptamer are referred to as "receptors". This DNA logic device sends signals based on cell surface sgc8c and sgc4f receptor expression by performing NOT, NOR, AND and OR logic operations, and amplifies and evaluates the signals using HCR. Meanwhile, the release of ICG from the endopore of HMSNs is controlled by affecting structural changes in the DNA logic device. This approach can accurately identify and treat multiple cells on demand based on the presence or absence of cell-specific receptors, facilitating the development of personalized medicine.

In situ detection of miRNA-21 in MCF-7 cell-derived extracellular vesicles using the red blood cell membrane vesicle strategy.

In this work, we constructed a novel membrane fusion strategy for extracellular vesicles (EVs) and red blood cell membrane vesicles (RVs). A nanoscale space is formed, which can improve the efficiency of the probe reaction with miRNA-21, which allows the in situ fluorescence detection of miRNA-21 in EVs.

Self-actuated biomimetic nanocomposites for photothermal therapy and PD-L1 immunosuppression.

Biomimetic nanocomposites are widely used in the biomedical field because they can effectively solve the problems existing in the current cancer treatment by realizing multi-mode collaborative treatment. In this study, we designed and synthesized a multifunctional therapeutic platform (PB/PM/HRP/Apt) with unique working mechanism and good tumor treatment effect. Prussian blue nanoparticles (PBs) with good photothermal conversion efficiency were used as nuclei and coated with platelet membrane (PM). The ability of platelets (PLTs) to specifically target cancer cells and inflammatory sites can effectively enhance PB accumulation at tumor sites. The surface of the synthesized nanocomposites was modified with horseradish peroxidase (HRP) to enhance the deep penetration of the nanocomposites in cancer cells. In addition, PD-L1 aptamer and 4T1 cell aptamer AS1411 were modified on the nanocomposite to achieve immunotherapy and enhance targeting. The particle size, UV absorption spectrum and Zeta potential of the biomimetic nanocomposite were determined by transmission electron microscope (TEM), Ultraviolet-visible (UV-Vis) spectrophotometer and nano-particle size meter, and the successful preparation was proved. In addition, the biomimetic nanocomposites were proved to have good photothermal properties by infrared thermography. The cytotoxicity test showed that it had a good killing ability of cancer cells. Finally, thermal imaging, tumor volume detection, immune factor detection and Haematoxilin-Eosin (HE) staining of mice showed that the biomimetic nanocomposites had good anti-tumor effect and could trigger immune response in vivo. Therefore, this biomimetic nanoplatform as a promising therapeutic strategy provides new inspiration for the current diagnosis and treatment of cancer.

Progress of Nonmetallic Electrocatalysts for Oxygen Reduction Reactions.

As a key role in hindering the large-scale application of fuel cells, oxygen reduction reaction has always been a hot issue and nodus. Aiming to explore state-of-art electrocatalysts, this paper reviews the latest development of nonmetallic catalysts in oxygen reduction reactions, including single atoms doped with carbon materials such as N, B, P or S and multi-doped carbon materials. Afterward, the remaining challenges and research directions of carbon-based nonmetallic catalysts are prospected.

Construction of nanocarriers based on nucleic acids and their applications in nanobiology delivery systems.

In recent years, nanocarriers based on nucleic acids have emerged as powerful and novel nanocarriers that are able to meet the demand for cancer-cell-specific targeting. Functional dynamics analysis revealed good biocompatibility, low toxicity and programmable structures, and their advantages include controllable size and modifiability. The development of novel hybrids has focused on the distinct roles of biosensing, drug and gene delivery, vaccine transport, photosensitization, counteracting drug resistance and functioning as carriers and logic gates. This review is divided into three parts: (i) DNA nanocarriers, (ii) RNA nanocarriers and (iii) DNA/RNA hybrid nanocarriers and their applications in nanobiology delivery systems. We also provide perspectives on possible future directions for growth in this field.

Nanomaterials based on thermosensitive polymer in biomedical field.

The progress of nanotechnology enables us to make use of the special properties of materials on the nanoscale and open up many new fields of biomedical research. Among them, thermosensitive nanomaterials stand out in many biomedical fields because of their "intelligent" behavior in response to temperature changes. However, this article mainly reviews the research progress of thermosensitive nanomaterials, which are popular in biomedical applications in recent years. Here, we simply classify the thermally responsive nanomaterials according to the types of polymers, focusing on the mechanisms of action and their advantages and potential. Finally, we deeply investigate the applications of thermosensitive nanomaterials in drug delivery, tissue engineering, sensing analysis, cell culture, 3D printing, and other fields and probe the current challenges and future development prospects of thermosensitive nanomaterials.