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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

Au-Fe3O4 nanoagent coated cell membrane for targeted delivery and enhanced chem/photo therapy.

Here, we propose a cancer cell membrane (CM) coated Au-Fe3O4 complex (AFTP@CM), loaded with tannic acid and phorbol 12-myristate 13-acetate for targeted drug delivery and enhanced chem/photo therapy.

Biomolecules in cell-derived extracellular vesicle chariots as warriors to repair damaged tissues.

In this review, we highlight the innovative applications of biomolecules from parent cell-derived extracellular vesicles (EVs) for tissue repair that have been developed in recent years. We evaluate the underlying mechanisms and therapeutic efficacy of each therapy. In previous literature reviews, it was most common to classify the use of EVs in tissue repair by disease type. This article reviews the role of three biomolecules in EVs in tissue repair. This review first summarizes the definitions and classifications of EVs. Then, the importance and significance of treating tissue damage with EVs are discussed. In particular, EV contents for tissue repair are three main types of biomolecules: proteins, RNAs and cell growth factors. The therapeutic and repair mechanisms of the biomolecules are discussed respectively. Finally, the development prospect and potential challenges of EV contents from highly differentiated cells as specific agents for tissue repair are summarized. When EVs are used to treat diseases such as tissue or organ damage, EVs play a role in delivery, and the real repair effect is effected by the various biomolecules carried by EVs. We believe that EV biomolecules have unparalleled advantages and clinical transformation potential for tissue repair and expect this review to inspire more intensive research work in this field.

The safety of echo contrast-enhanced ultrasound in high-intensity focused ultrasound ablation for abdominal wall endometriosis: a retrospective study.

BACKGROUND: We aimed to investigate the efficacy and safety of echo contrast-enhanced ultrasound (CEUS) during high-intensity focused ultrasound (HIFU) ablation therapy for abdominal wall endometriosis (AWE). METHODS: A total of 67 patients with AWE were treated with HIFU ablation, and their demographic characteristics were retrospectively analysed. Blood perfusion of the focal lesion was assessed before the operation, during ablation and after the operation with the use of an ultrasound contrast agent, and the effect of the ultrasound contrast agent on treatment was assessed over a 1-year follow-up period. The degree of symptom relief and adverse effects were evaluated after HIFU ablation. RESULTS: Eighty-two lesions were ablated in 67 patients. CEUS showed that all lesions were successfully ablated with HIFU. The shrinkage ratio of the lesions significantly increased over the follow-up period. Intermittent pain disappeared at 1 month after the operation, and the patients' pain scores significantly decreased at the 1-year follow-up. The mean [± standard deviation (SD)] lesion volume was 7.64±8.95 cm3 on B-mode ultrasound. The post-HIFU non-perfused volume was 18.34±24.08 cm3, and the rate of massive changes on greyscale imaging was 96.16%±5.44% at 12 months. During the procedure, the main complications were a prickling sensation and tenderness in the treatment area and/or a transient "hot" sensation on the skin. After the procedure, there was no obvious discomfort except for pain. Two patients developed an approximately 1-cm area of skin that exhibited a waxy appearance. Seven patients had haematuria. No severe complications were observed. CONCLUSIONS: Ultrasound contrast agents are effective and safe for evaluating the effect of HIFU ablation on AWE, and this approach provides significant guidance and evaluation benefits for the use of HIFU treatment for AWE without obvious side effects.

Co-biomembrane-coated Fe3O4/MnO2 multifunctional nanoparticles for targeted delivery and enhanced chemodynamic/photothermal/chemo therapy.

Here, the co-membrane system of MCF-7 breast cancer cell membrane (MM) and Escherichia coli membrane (EM)-coated Fe3O4/MnO2 multifunctional composite nanoparticles loaded with DOX (Fe3O4/MnO2/MM/EM/D) was used for targeted drug delivery and biological imaging.

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.

Self-assembled peptide nanoparticles with endosome escaping permits for co-drug delivery.

The diagnosis and treatment of major diseases, especially tumors, was the key to improving the cure rate and survival rate of patients. Therefore, one of the main goals of modern medicine was to develop effective, non-toxic treatments. This paper successfully established dipeptide nanoparticles/clofarabine/aptamer AS1411/influenza hemagglutinin peptide/siRNA/doxorubicin (DNPs/Clolar/AS1411/HA/RNA/DOX) multi-functional nanoparticles for specific delivery, cancer treatment and bioimaging. It was an ideal choice for multi-drug synergy treatment. First, non-toxic DNPs formed by self-assembly of dipeptides with safe and biocompatible effect. Second, from the perspective of the multi-functional nanoparticles for nano-drug tumors imaging monitoring, AS1411 and HA were used as cell permits for enhancing the specificity of cell drug delivery ability and improving the endosomal escape, respectively. Third, the multi-functional nanoparticles with Clolar, siRNA and DOX, three drug synergistic treatments were used to improve the therapeutic effect of tumors. Both cell experiments and vivo experiments demonstrated that the synergistic treatment of the multi-drugs was superior to the effect of single-drug therapy. Thus, the proposed multi-functional nanoparticles have initiated new ideas for these hybrid anticancer drugs based on peptide self-assembled nanocarriers and its widely applications in biomedicine.

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+.

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.

Ternary Z-scheme heterojunction of Bi SPR-promoted BiVO4/g-C3N4 with effectively boosted photoelectrochemical activity for constructing oxytetracycline aptasensor.

Developing photoactive materials with wide spectral response is critical to improve the sensitivity of PEC biosensors. Herein, a sensitive photoelectrochemical (PEC) aptasensor was fabricated based on Bi surface plasmon resonance (SPR)-promoted BiVO4/g-C3N4 (Bi/BiVO4/g-C3N4) as photoactive material for the detection of oxytetracycline (OTC). Ternary Z-scheme Bi/BiVO4/g-C3N4 heterojunction exhibited widest spectral response and best PEC activity compared to g-C3N4, BiVO4, Bi/BiVO4, and BiVO4/g-C3N4. The wide spectral response and high PEC activity could be attributed to three reasons: Firstly, the SPR effect of Bi could greatly increase light harvesting; Secondly, Bi served as an electron conduction bridge between BiVO4 and g-C3N4 to form Z-scheme structure, significantly accelerating the separation of photogenerated carriers; Thirdly, the synergism of Z-scheme heterojunction and the SPR effect of Bi efficiently boosted the photoelectric response. Based on the above sensitization strategies, the proposed PEC aptasensor for OTC determination showed a wide linear range of 0.01-1000 nM and a low detection limit (S/N = 3) of 3.3 × 10-3 nM. Moreover, the high stability, satisfactory repeatability and favorable practicability of the fabricated PEC aptasensor revealed the potential applications for accurate monitoring of antibiotics in environmental media.