Spatially confined CuFe2O4 nanosphere in N/O-codoped porous carbon mimetics for triple-mode sensing of antibiotics and visual detection of neurotransmitters in biofluids.

BACKGROUND: Carbon-based nanozymes have recently received enormous concern, however, there is still a huge challenge for inexpensive and large-scale synthesis of magnetic carbon-based "Two-in-One" mimics with both peroxidase (POD)-like and laccase-like activities, especially their potential applications in multi-mode sensing of antibiotics and neurotransmitters in biofluids. Although some progresses have been made in this field, the feasibility of biomass-derived carbon materials with both POD-like and laccase-like activities by polyatomic doping strategy is still unclear. In addition, multi-mode sensing platform can provide a more reliable result because of the self-validation, self-correction and mutual agreement. Nevertheless, the use of magnetic carbon-based nanozyme sensors for the multi-mode detection of antibiotics and neurotransmitters have not been investigated. RESULTS: We herein report a shrimp shell-derived N, O-codoped porous carbon confined magnetic CuFe2O4 nanosphere with outstanding laccase-like and POD-like activities for triple-mode sensing of antibiotic d-penicillamine (D-PA) and chloramphenicol (CPL), as well as colorimetric detection of neurotransmitters in biofluids. The magnetic CuFe2O4/N, O-codoped porous carbon (MCNPC) armored mimetics was successfully fabricated using a combined in-situ coordination and high-temperature crystallization method. The synthesized MCNPC composite with superior POD-like activity can be used for colorimetric/temperature/smartphone-based triple-mode detection of D-PA and CPL in goat serum. Importantly, the MCNPC nanozyme can also be used for colorimetric analysis of dopamine and epinephrine in human urine. SIGNIFICANCE: This work not only offered a novel strategy to large-scale, cheap synthesize magnetic carbon-based "Two-in-One" armored mimetics, but also established the highly sensitive and selective platforms for triple-mode monitoring D-PA and CPL, as well as colorimetric analysis of neurotransmitters in biofluids without any tanglesome sample pretreatment.

Accelerated diagnosis: a crosslinking catalytic hairpin assembly system for rapid and sensitive SARS-CoV-2 RNA detection.

The COVID-19 pandemic has underscored the urgent need for rapid and reliable strategies for early detection of SARS-CoV-2. In this study, we propose a DNA nanosphere-based crosslinking catalytic hairpin assembly (CCHA) system for the rapid and sensitive SARS-CoV-2 RNA detection. The CCHA system employs two DNA nanospheres functionalized with catalytic hairpin assembly (CHA) hairpins. The presence of target SARS-CoV-2 RNA initiated the crosslinking of DNA nanospheres via CHA process, leading to the amplification of fluorescence signals. As a result, the speed of SARS-CoV-2 diagnosis was enhanced by significantly increasing the local concentration of the reagents in a crosslinked DNA product, leading to a detection limit of 363 fM within 5 min. The robustness of this system has been validated in complex environments, such as fetal bovine serum and saliva. Hence, the proposed CCHA system offers an efficient and simple approach for rapid detection of SARS-CoV-2 RNA, holding substantial promise for enhancing COVID-19 diagnosis.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

Trace Amount of Bi-Doped Core-Shell Pd@Pt Mesoporous Nanospheres with Specifically Enhanced Peroxidase-Like Activity Enable Sensitive and Accurate Detection of Acetylcholinesterase and Organophosphorus Nerve Agents.

The urgent need for sensitive and accurate assays to monitor acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs) arises from the imperative to safeguard human health and protect the ecosystem. Due to its cost-effectiveness, ease of operation, and rapid response, nanozyme-based colorimetry has been widely utilized in the determination of AChE activity and OPs. However, the rational design of nanozymes with high activity and specificity remains a great challenge. Herein, trace amount of Bi-doped core-shell Pd@Pt mesoporous nanospheres (Pd@PtBi2) have been successfully synthesized, exhibiting good peroxidase-like activity and specificity. With the incorporation of trace bismuth, there is a more than 4-fold enhancement in the peroxidase-like performance of Pd@PtBi2 compared to that of Pd@Pt. Besides, no significant improvement of oxidase-like and catalase-like activities of Pd@PtBi2 was found, which prevents interference from O2 and undesirable consumption of substrate H2O2. Based on the blocking impact of thiocholine, a colorimetric detection platform utilizing Pd@PtBi2 was constructed to monitor AChE activity with sensitivity and selectivity. Given the inhibition of OPs on AChE activity, a biosensor was further developed by integrating Pd@PtBi2 with AChE to detect OPs, capitalizing on the cascade amplification strategy. The OP biosensor achieved a detection limit as low as 0.06 ng mL-1, exhibiting high sensitivity and anti-interference ability. This work is promising for the construction of nanozymes with high activity and specificity, as well as the development of nanozyme-based colorimetric biosensors.

Multi-level Reactive Oxygen Species Amplifier to Enhance Photo-/Chemo-Dynamic/Ca2+ Overload Synergistic Therapy.

Reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) hold great promise for tumor treatment. However, hypoxia, insufficient H2O2, and overexpressed glutathione (GSH) in the tumor microenvironment (TME) hinder ROS generation significantly. Herein, we reported CaO2@Cu-TCPP/CUR with O2/H2O2/Ca2+ self-supply and GSH depletion for enhanced PDT/CDT and Ca2+ overload synergistic therapy. CaO2 nanospheres were first prepared and used as templates for guiding the coordination between the carboxyl of tetra-(4-carboxyphenyl)porphine (TCPP) and Cu2+ ions as hollow CaO2@Cu-TCPP, which facilitated GSH-activated TCPP-based PDT and Cu+-mediated CDT. The hollow structure was then loaded with curcumin (CUR) to form CaO2@Cu-TCPP/CUR composites. Cu-TCPP prevented degradation of CaO2, while Cu2+ ions reacted with GSH to deplete GSH, produce Cu+ ions, and release TCPP, CaO2, and CUR. CaO2 reacted with H2O to generate O2, H2O2, and Ca2+ to achieve O2/H2O2/Ca2+ self-supply for TCPP-based PDT, Cu+-mediated CDT, and CUR-enhanced Ca2+ overload therapy. Thus, this multilevel ROS amplifier enhances synergistic therapy with fewer side effects and drug resistance.

Target proteins-regulated DNA nanomachine-electroactive substance complexes enable separation-free electrochemical detection of clinical exosome.

Simple and reliable profiling of tumor-derived exosomes (TDEs) holds significant promise for the early detection of cancer. Nonetheless, this remains challenging owing to the substantial heterogeneity and low concentration of TDEs. Herein, we devised an accurate and highly sensitive electrochemical sensing strategy for TDEs via simultaneously targeting exosomal mucin 1 (MUC1) and programmed cell death ligand 1 (PD-L1). This approach employs high-affinity aptamers as specific recognition elements, utilizes rolling circle amplification and DNA nanospheres as effective bridges and signal amplifiers, and leverages methylene blue (MB) and doxorubicin (DOX) as robust signal reporters. The crux of this separation- and label-free method is the specific response of MB and DOX to G-quadruplex structures and DNA nanospheres, respectively. Quantifying TDEs using this strategy enabled precise discrimination of lung cancer patients (n = 25) from healthy donors (n = 12), showing 100% specificity (12/12), 92% sensitivity (23/25), and an overall accuracy of 94.6% (35/37), with an area under the receiver operating characteristic curve (AUC) of 0.97. Furthermore, the assay results strongly correlated with findings from computerized tomography and pathological analyses. Our approach could facilitate the early diagnosis of lung cancer through TDEs-based liquid biopsy.

Oxygen Vacancy-Rich Bimetallic Au@Pt Core-Shell Nanosphere-Functionalized Electrospun ZnFe2O4 Nanofibers for Chemiresistive Breath Acetone Detection.

Sensitive and selective acetone detection is of great significance in the fields of environmental protection, industrial production, and individual health monitoring from exhaled breath. To achieve this goal, bimetallic Au@Pt core-shell nanospheres (BNSs) functionalized-electrospun ZnFe2O4 nanofibers (ZFO NFs) are prepared in this work. Compared to pure NFs-650 analogue, the ZFO NFs/BNSs-2 sensor exhibits a stronger mean response (3.32 vs 1.84), quicker response/recovery speeds (33 s/28 s vs 54 s/42 s), and lower operating temperature (188 vs 273 °C) toward 0.5 ppm acetone. Note that an experimental detection limit of 30 ppb is achieved, which ranks among the best cases reported thus far. Besides the demonstrated excellent repeatability, humidity-enhanced response, and long-term stability, the selectivity toward acetone is remarkably improved after BNSs functionalization. Through material characterizations and DFT calculations, all these improvements could be attributed to the boosted oxygen vacancies and abundant Schottky junctions between ZFO NFs and BNSs, and the synergistic catalytic effect of BNSs. This work offers an alternative strategy to realize selective subppm acetone under high-humidity conditions catering for the future requirements of noninvasive breath diabetes diagnosis in the field of individual healthcare.

Chitosan-based hybrid nanospheres for vessel normalization towards enhancing tumor chemotherapy.

Vessel normalization has proved imperative in tumor growth inhibition. In this work, biopolymer-based hybrid nanospheres capable of normalizing blood vessels were designed to improve the therapeutic effect of chemotherapeutic drugs. Zn0.4Fe2.6O4 nanoparticles (ZFO NPs) were synthesized, and were encapsulated in cross-inked chitosan (CS) along with a nitric oxide (NO) precursor, DETA NONOate, forming hybrid ZFO/NO@CS nanospheres highly stable in physiological environment. The structure, morphology and size of the nanospheres were characterized. The ZFO/NO@CS nanospheres could release NO under acidic conditions typical of intratumoral and intracellular environment. The results of related factors expression, wound healing and tube formation assays demonstrated that both the encapsulated ZFO NPs and the released NO were able to inhibit angiogenesis in tumors. The ZFO/NO@CS nanospheres enhanced the antitumor efficacy of the chemotherapeutic drug DOX by normalizing tumor vessels, as evidenced by in vivo experiments for CT26 tumor-bearing mice. By analyzing the contents of Fe in the tumor and different organs, the nanospheres were found to accumulate primarily at the tumor site. The blood analysis showed little side effect of the nanospheres. The ZFO/NO@CS nanospheres have great potential in improving tumor therapeutic effect when used in combination with chemotherapeutic drugs.

Facile fabricate sandwich-structured molecularly imprinted dopamine polymer for simultaneously specific capture of Low-density lipoprotein and eliminate "bad cholesterol".

A simplified approach for preparation of sandwich type molecularly imprinted polymers (PPDA-MIPs) is proposed for simultaneously identify Low-density lipoprotein (LDL) and dispose "bad cholesterol". Porous polydopamine nanosphere (PPDA) is applied as a matrix for immobilization of LDL, and the imprinted layer is formed by dopamine acting as a functional monomer. Since imprinted cavities exhibit shape memory effects in terms of recognizing selectivity, the PPDA-MIPs exhibit excellent selectivity toward LDL and a substantial binding capacity of 550.3 µg mg-1. Meanwhile, six adsorption/desorption cycles later, the adsorption efficiency of 83.09 % is still achieved, indicating the adequate stability and reusability of PPDA-MIPs. Additionally, over 80 % of cholesterol is recovered, indicating the completeness of "bad cholesterol" removal in LDL. Lastly, as demonstrated by gel electrophoresis, PPDA-MIPs performed satisfactory behavior for the removal of LDL from the goat serum sample.

Investigation of folate-modified EGCG-loaded thermosensitive nanospheres inducing immunogenic cell death and damage-associated molecular patterns in hepatocellular carcinoma.

BACKGROUND: The systemic treatment of advanced hepatocellular carcinoma is currently facing a bottleneck. EGCG, the primary active compound in green tea, exhibits anti-tumor effects through various pathways. However, there is a lack of study on EGCG-induced immunogenic cell death (ICD) in hepatocellular carcinoma. METHODS: In a previous study, we successfully synthesized folate-modified thermosensitive nano-materials, encapsulated EGCG within nanoparticles using a hydration method, and established the EGCG nano-drug delivery system. The viability of HepG2 cells post-EGCG treatment was assessed via the MTT and EdU assays. Cell migration and invasion were evaluated through wound healing experiments, Transwell assays, and Annexin V-FITC/PI assay for apoptosis detection. Additionally, the expression levels of damage-associated molecular patterns (DAMPs) were determined using immunofluorescence, ATP measurement, RT-qPCR, and Western Blot. RESULTS: The drug sensitivity test revealed an IC50 value of 96.94 µg/mL for EGCG in HepG2 cells after 48 h. EGCG at a low concentration (50 µg/mL) significantly impeded the migration and invasion of HepG2 cells, showing a clear dose-dependent response. Moreover, medium to high EGCG concentrations induced cell apoptosis in a dose-dependent manner and upregulated DAMPs expression. Immunofluorescence analysis demonstrated a notable increase in CRT expression following low-concentration EGCG treatment. As EGCG concentration increased, cell viability decreased, leading to CRT exposure on the cell membrane. EGCG also notably elevated ATP levels. RT-qPCR and Western Blot analyses indicated elevated expression levels of HGMB1, HSP70, and HSP90 following EGCG intervention. CONCLUSION: EGCG not only hinders the proliferation, migration, and invasion of hepatocellular carcinoma cells and induces apoptosis, but also holds significant clinical promise in the treatment of malignant tumors by promoting ICD and DAMPs secretion.

"Cave Effect" Induces Self-Assembled Bimetallic Hollow Structure for Three-in-One Lateral Flow Immunoassay.

Bimetallic hollow structures have attracted much attention due to their unique properties, but they still face the problems of nonuniform alloys and excessive etching leading to structural collapse. Here, uniform bimetallic hollow nanospheres are constructed by pore engineering and then highly loaded with hemin (Hemin@MOF). Interestingly, in the presence of polydopamine (PDA), the competitive coordination between anionic polymer (γ-PGA) and dimethylimidazole does not lead to the collapse of the external framework but self-assembly into a hollow structure. By constructing the Hemin@MOF immune platform and using E. coli O157:H7 as the detection object, we find that the visual detection limits can reach 10, 3, and 3 CFU/mL in colorimetric, photothermal, and catalytic modes, which is 4 orders of magnitude lower than the traditional gold standard. This study provides a new idea for the morphological modification of the metal-organic skeleton and multifunctional immunochromatography detection.

TiO2 nanorod decorated with MoS2 nanospheres: An efficient dual-functional photocatalyst for antibiotic degradation and hydrogen production.

The design and preparation of dual-functional photocatalysts for simultaneously realizing photocatalytic wastewater purification and hydrogen energy generation pose significant challenges. This article presents the engineering of a binary heterostructured photocatalyst by combining TiO2 (nanorods) and MoS2 nanosphere using a straightforward solvothermal method and the assessment of the phase structures, morphologies, and optical properties of the resulting nanocomposites using diverse analytical techniques. The TiO2(Rod)/MoS2 composite exhibits remarkable efficacy in degrading ciprofloxacin, achieving 93% removal rate within 1 h, which is four times higher than that of bare TiO2. Moreover, the optimized TiO2(Rod)/MoS2 presents an outstanding hydrogen production rate of 7415 µmol g-1, which is ∼24 times higher than that of pristine TiO2. Under UV-visible light irradiation, the TiO2(Rod)/MoS2 heterojunction displays an exceptional photocatalytic performance in terms of both photodegradation and hydrogen production, surpassing the performance of TiO2 particle/MoS2. The study findings demonstrate that TiO2(Rod)/MoS2 nanocomposites exhibit considerably improved photocatalytic degradation and hydrogen generation activities. Based on the experimental results, a possible mechanism is proposed for the transfer and separation of charge carriers in Z-scheme heterojunctions.

A novel seawater hydrothermal-deep eutectic solvent pretreatment enhances the production of fermentable sugars and tailored lignin nanospheres from Pinus massoniana.

Lignocellulose biorefinery depended on effective pretreatment strategies is of great significance for solving the current global crisis of ecosystem and energy security. This study proposes a novel approach combining seawater hydrothermal pretreatment (SHP) and microwave-assisted deep eutectic solvent (MD) pretreatment to achieve an effective fractionation of Pinus massoniana into high value-added products. The results indicated that complex ions (Mg2+, Ca2+, and Cl-) in natural seawater served as Lewis acids and dramatically promoted the depolymerization of mannose and xylan into oligosaccharides with 40.17 % and 75.43 % yields, respectively. Subsequent MD treatment realized a rapid and effective lignin fractionation (~90 %) while retaining cellulose. As a result, the integrated pretreatment yielded ~85 % of enzymatic glucose, indicating an eightfold increase compared with untreated pine. Because of the increased hydrophobicity induced by the formation of acyl groups during MD treatment, uniform lignin nanospheres were successfully recovered from the DES. It exhibited low dispersibility (PDI = 2.23), small molecular weight (1889 g/mol), and excellent oxidation resistance (RSI = 5.94), demonstrating promising applications in functional materials. The mechanism of lignin depolymerization was comprehensively elucidated via FTIR, 2D-HSQC NMR, and GPC analyses. Overall, this study provides a novel and environmentally friendly strategy for lignocellulose biorefinery and lignin valorization.

Treatment of peri-implantitis using nonsurgical debridement combined with bioresorbable doxycycline nanospheres: a case report with 3-year follow-up.

Treatment of peri-implant diseases focuses on reducing the bacterial load and consequent infection control. The use of local antimicrobials as an adjunct to mechanical therapy may result in a better outcome. Among antimicrobials, doxycycline stands out because of its local modulation of cytokines, microbial reduction, and clinical parameters in the treatment of periodontal diseases. The objective of this case report was to describe the combined application of mechanical debridement and bioresorbable doxycycline-loaded nanospheres for the treatment of peri-implantitis in a 71-year-old man. At the 3-year evaluation, the peri-implant tissues had improved, showing decreased probing depths, an absence of bleeding on probing, and no suppuration. This case report highlights the importance of supportive therapy, which is essential for the long-term success of peri-implantitis treatment.

Mussel-inspired interface deposition strategy for mesoporous metal-phenolic nanospheres with superior antioxidative, photothermal and antibacterial performance.

Metal-phenolic networks (MPNs) have emerged as a versatile and multifunctional platform applied in bioimaging, disease treatment, electrocatalysis, and water purification. The synthesis of MPNs with mesoporous frameworks and ultra-small diameters (<200 nm), crucial for post-modification, cargo loading, and mass transport, remains a formidable challenge. Inspired by mussel chemistry, mesoporous metal-phenolic nanospheres (MMPNs) are facilely prepared by direct deposition of the metal-polyphenol complex on the interface of oil nano-droplets composed of block copolymers/1,3,5-trimethylbenzene followed by a spontaneous template-removal process. Due to the penetrable and stable networks, the oil nano-droplets gradually leak from the networks driven by shear stress during the stirring process. As a result, MMPNs are obtained without additional template removal procedures such as solvent extraction or high-temperature calcination. The materials have a large pore size (∼12.1 nm), uniform spherical morphology with a small particle size (∼99 nm), and a large specific surface area (49.8 m2 g-1). Due to the abundant phenolic hydroxyl groups, the MMPNs show excellent antioxidative property. The MMPNs also have excellent photothermal property, whose photothermal conversion efficiency was 40.9 %. Moreover, the phenolic hydroxyl groups can reduce Ag+ in situ to prepare Ag nanoparticles loaded MMPNs composites, which have excellent inhibition performance of drug-resistant bacteria biofilm.

Dual-signal amplified electrochemical aptasensor based on Au/MrGO and DNA nanospheres for ultra-sensitive detection of BPA without directly modified working electrode.

Rapid and sensitive analysis of bisphenol A (BPA) is essential for preventing health risks to humans and animals. Hence, a signal-amplified electrochemical aptasensor without repetitive polishing and modification of working electrode was developed for BPA using Au-decorated magnetic reduced graphene oxide (Au/MrGO)-based recognition probe (RP) and DNA nanospheres (DNS)-based signal probe (SP) cooperative signal amplification. The DNS served as a signal molecule carrier and signal amplifier, while Au/MrGO acted as a signal amplifier and excellent medium for magnetic adsorption and separation. Moreover, utilizing the excellent magnetic properties of Au/MrGO eliminates the need for repetitive polishing and multi-step direct modification of the working electrode while ensuring that all detection processes take place in solution and that used Au/MrGO can be easily recycled. The proposed aptasensor exhibited not only good stability and selectivity, but also excellent sensitivity with a limit of detection (LOD) of 8.13 fg/mL (S/N = 3). The aptasensor's practicality was proven by spiking recovery tests on actual water samples and comparing the results with those detected by HPLC. The excellent sensitivity and selectivity make this aptasensor an alternative and promising avenue for rapid detection of BPA in environmental monitoring.

Highly selective nanozyme-based glucose sensing platform via construction of artificial recognition sites on gold nanospheres.

Nanozymes have been regarded as the ideal alternatives to natural enzymes in bioassays due to their good stability and low cost. However, their applications in sensing usually suffer from poor selectivity. For example, Au-based nanozymes, as a kind of classical glucose oxidase mimic enzyme, could catalyze diverse monosaccharides. Therefore, it is of great necessity and urgency to endow the Au-based nanozymes with enhanced selectivity for the construction of specific glucose sensing platform. In our study, easily recyclable polydopamine (PDA)-supported Au-based nanozymes (PDA@Au NPs) were successfully prepared and could catalyze diverse monosaccharides including glucose, xylose, mannose, and sucrose. To enhance the selectivity of PDA@Au NPs, molecularly imprinted polymers (MIPs) were constructed on the surface of PDA@Au NPs using glucose and boronic acid derivatives as template and functional monomer. Impressively, the catalytic activity of the obtained molecularly imprinted nanozyme (PDA@Au NPs-MIPs) only shows a slight decrease (6.3%) while their selectivity is obviously enhanced (≥230%). Accordingly, the as-prepared sensor achieved the sensitive and selective detection of glucose in the concentration range of 10 µM-1 mM and a low detection limit (LOD) of 0.227 µM (S/N = 3), avoiding the influence of other monosaccharides exited in the sensing solutions to a great extent. As expected, the as-prepared sensors also showed good recovery, and long-term stability.

Mesoporous silica nanospheres-mediated insecticide and antibiotics co-delivery system for synergizing insecticidal toxicity and reducing environmental risk of insecticide.

Mesoporous silica nanoparticles (MSNs) are efficient carriers of drugs, and are promising in developing novel pesticide formulations. The cotton aphids Aphis gossypii Glover is a world devastating insect pest. It has evolved high level resistance to various insecticides thus resulted in the application of higher doses of insecticides, which raised environmental risk. In this study, the MSNs based pesticide/antibiotic delivery system was constructed for co-delivery of ampicillin (Amp) and imidacloprid (IMI). The IMI@Amp@MSNs complexes have improved toxicity against cotton aphids, and reduced acute toxicity to zebrafish. From the 16S rDNA sequencing results, Amp@MSNs, prepared by loading ampicillin to the mesoporous of MSNs, greatly disturbed the gut community of cotton aphids. Then, the relative expression of at least 25 cytochrome P450 genes of A. gossypii was significantly suppressed, including CYP6CY19 and CYP6CY22, which were found to be associated with imidacloprid resistance by RNAi. The bioassay results indicated that the synergy ratio of ampicillin to imidacloprid was 1.6, while Amp@MSNs improved the toxicity of imidacloprid by 2.4-fold. In addition, IMI@Amp@MSNs significantly improved the penetration of imidacloprid, and contributed to the amount of imidacloprid delivered to A. gossypii increased 1.4-fold. Thus, through inhibiting the relative expression of cytochrome P450 genes and improving penetration of imidacloprid, the toxicity of IMI@Amp@MSNs was 6.0-fold higher than that of imidacloprid. The greenhouse experiments further demonstrated the enhanced insecticidal activity of IMI@Amp@MSNs to A. gossypii. Meanwhile, the LC50 of IMI@Amp@MSNs to zebrafish was 3.9-fold higher than that of IMI, and the EC50 for malformation was 2.8-fold higher than IMI, respectively, which indicated that the IMI@Amp@MSNs complexes significantly reduced the environmental risk of imidacloprid. These findings encouraged the development of pesticide/antibiotic co-delivery nanoparticles, which would benefit pesticide reduction and environmental safety.

DNA Nanospheres Assisted Spatial Confinement Signal Amplification for MicroRNA Imaging in Live Cancer Cells.

DNA assemblies are commonly used in biosensing, particularly for the detection and imaging of microRNAs (miRNAs), which are biomarkers associated with tumor progression. However, the difficulty lies in the exploration of high-sensitivity analytical techniques for miRNA due to its limited presence in living cells. In this study, we introduced a DNA nanosphere (DS) enhanced catalytic hairpin assembly (CHA) system for the detection and imaging of intracellular miR-21. The single-stranded DNA with four palindromic portions and extending sequences at the terminal was annealed for assembling DS, which avoided the complex sequence design and high cost of long DNA strands. Benefiting from the multiple modification sites of DS, functional hairpins H1 (modified with Cy3 and BHQ2) and H2 were grafted onto the surface of DS for assembling DS-H1-H2 using a hybridization reaction. The DS-H1-H2 system utilized spatial confinement and the CHA reaction to amplify fluorescence signals of Cy3. This enabled highly sensitive and rapid detection of miR-21 in the range from 0.05 to 3.5 nM. The system achieved a limit of determination (LOD) of 2.0 pM, which was 56 times lower than that of the control CHA circuit with freedom hairpins. Additionally, the sensitivity was improved by 8 times. Moreover, DS-H1-H2 also showed an excellent imaging capability for endogenous miR-21 in tumor cells. This was due to enhanced cell internalization efficiency, accelerated reaction kinetics, and improved biostability. The imaging strategy was shown to effectively monitor the dynamic content of miR-21 in live cancer cells and differentiate various cells. In general, the simple nanostructure DS not only enhanced the detection and imaging capability of the conventional probe but also could be easily integrated with the reported DNA-free probe, indicating a wide range of potential applications.

A nitrogen-doped hollow carbon nanospheres-based aptasensor for non-invasive salivary detection of progesterone.

Developing an easy-to-use and non-invasive sensor for monitoring progesterone (P4) as a multi-functional hormone is highly demanded for point-of-care testing. In this study, an ultrasensitive electrochemical aptasensor is fabricated for monitoring P4 in human biofluids. The sensing interface was designed based on the porous nitrogen-doped hollow carbon spheres (N-HCSs). The N-HCSs covalently immobilized high-dense aptamer (Apt) sequences as the bioreceptor of P4. The electron transfer of the redox probe was hindered by incubating P4 on the aptasensor surface and forming the P4-Apt complexes. Meanwhile, the signaling was decreased under two wide linear dynamic ranges (LDRs) from 10 fM to 5.6 µM with a limit of detection (LOD) value of 3.33 fM. The aptasensor presented satisfactory selectivity in the presence of different off-target species with successful feasibility for P4 detection in some human urine and saliva samples. The aptasensor with high sensitivity, as an advantage for on-site and sensitive measurement of P4, can be considered a non-invasive tool for routine analysis of real-world clinical samples method.