NIR-Actuated Targeted Janus Nanomotors Remodel Immunosuppressive Tumor Microenvironment for Augmented Cancer Immunotherapy.

Tumor-associated macrophages (TAMs) always display immunosuppressive M2 phenotype in the tumor microenvironment to facilitate tumor growth, invasion, and metastasis. Ibrutinib (IBR), a novel irreversible Bruton's tyrosine kinase (BTK) inhibitor, has been employed to repolarize the BTK-overexpressed TAMs from M2 to M1 phenotype to remodel the immunosuppressive tumor microenvironment. However, the poor solubility of IBR extremely hinders its bioavailability, which results in low tumor accumulation and TAMs uptake in vivo. Herein, NIR laser-actuated Janus nanomotors are proposed for the effective and deep delivery of IBR to TAMs in solid tumor for targeted immunotherapy. Under NIR irradiation, the Janus nanomotors exhibit efficient photothermal conversion to produce powerful propulsion via self-thermophoresis with a speed of 12.15 µm s-1 . Combined with the salic acid targeting and IBR loading, the nanomotors significantly boost their binding and uptake efficacy by M2-like macrophages during the active motion, which highly facilitate the reprogramming of M2 to M1 macrophages in vitro. Furtherly, the autonomous motion also validly improves in vivo accumulation and penetration depth in tumors to alter the M1/M2 polarization balance and activate T cells. Overall, the synthesized IC@MSA JNMs would provide a promising strategy for the efficient delivery of immunological agents toward targeted cancer immunotherapy.

Multifunctional Biotemplated Micromotors for In Situ Decontamination of Antibiotics and Heavy Metals in Soil and Groundwater.

The ubiquitous pollution by antibiotics and heavy metal ions has posed great threats to human health and the ecological environment. Therefore, we developed a self-propelled tubular micromotor based on natural fibers as an active heterogeneous catalyst for antibiotic degradation and adsorbent for heavy metal ions in soil/water. The prepared micromotors can move in the presence of hydrogen peroxide (H2O2) through a bubble recoil mechanism. The MnO2 NPs and MnFe2O4 NPs loaded on the hollow fibers not only enabled self-driven motion and magnetic control but also served as activators of peroxymononsulfate (PMS) and H2O2 to produce active free radicals SO4•- and •OH. Benefiting from the self-propulsion and bubble generation, the micromotors can effectively overcome the disadvantage of low diffusivity of traditional heterogeneous catalysts, achieving the degradation of more than 90% TC in soil within 30 min. Meanwhile, due to the large specific surface area, abundant active sites, and strong negative zeta potential, the micromotors can effectively adsorb heavy metal ions in the water environment. In 120 min, self-propelled micromotors removed more than 94% of lead ions, an increase of 47% compared to static micromotors, illustrating the advantages of on-the-fly capture. The prepared micromotors with excellent catalytic performance and adsorption capacity can simultaneously degrade antibiotics and adsorb heavy metal ions. Moreover, the magnetic response enabled the micromotors to be effectively separated from the system after completion of the task, avoiding the problem of secondary pollution. Overall, the proposed micromotors provide a new approach to the utilization of natural materials in environmental applications.

Dual-source powered nanomotors coupled with dual-targeting ligands for efficient capture and detection of CTCs in whole blood and in vivo tumor imaging.

Circulating tumor cells (CTCs) are important biomarkers in cancer diagnosis. However, the specific labeling of CTCs with high capture efficiency in whole blood remains a problem. Herein, a dual-source-driven nanomotor coupled with dual-targeting ligands (CD@NM) was designed for efficient capture, specific imaging and quantitative detection of CTCs. In both water and biological fluid, CD@NMs moved autonomously under the propulsion of a magnetic field and H2O2 solution, which improved the capture efficiency of CTCs to 97.50 ± 2.38%. More importantly, specific labeling of CTCs was achieved by fluorescence quenching and recovery of fluorescent carbon dots modified on the CD@NMs. As a result, the CD@NMs exhibited efficient CTC capture, specific CTC imaging and recognition in whole blood. CD@NMs were also successfully deployed in the specific imaging of tumor tissues in vivo. On this basis, CD@NMs are expected to provide a new platform for tumor diagnosis both in vitro and in vivo.

Dual-Modal Lateral Flow Test Strip Assisted by Near-Infrared-Powered Nanomotors for Direct Quantitative Detection of Circulating MicroRNA Biomarkers from Serum.

Quantification of microRNA (miRNA) has attracted intense interest owing to its importance as a biomarker for the early diagnosis of multiple diseases. However, the inefficient capture of microRNAs from complex biological samples due to the passive diffusion of detection probes essentially restricts their accurate quantification. Herein, we report near-infrared (NIR)-powered Janus nanomotors composed of Au nanorods and periodic mesoporous organo-silica microspheres (AuNR/PMO JNMs) as "swimming probes" to assist a lateral flow test strip (LFTS) for direct, amplification-free, and quantitative miRNA-21 detection in serum and cell medium. The AuNR/PMO JNMs were conjugated with designed hDNA as a recognition probe for miRNA-21. Under NIR irradiation, the exposed AuNRs can generate asymmetric thermal gradients around the JNMs to achieve vigorous self-propelled thermophoretic motion. The active movement significantly accelerated the recognition of miRNA-21 targets, which greatly improved the capture efficiency from 59.39 to 86.12% in the reaction buffer. The enhanced miRNA-21 capture enabled direct quantitative miRNA-21 detection on the LFTS assay with both visual and thermal signals. Under the assistance of AuNR/PMO JNMs, a limit-of-detection of 18 fmol/L for miRNA-21 was achieved, which was 12.22-fold compared to that of LFTS assay with static probes. The constructed LFTS assay was further successfully deployed to directly sense the miRNA-21 in spiked serum samples and MDA-MB-231 medium. Overall, the AuNR/PMO JNM-assisted LFTS system unveils a concrete point-of-care testing strategy for precise miRNA detection in real biological samples, which holds great potential for early diagnosis and treatment of miRNA-related diseases.

An immunoassay based on nanomotor-assisted electrochemical response for the detection of immunoglobulin.

An immunoassay strategy has been developed based on nanomotor-assisted electrochemical measurements for simple and sensitive detection of immunoglobulin (IgG). The self-propelled Fe3O4@SiO2/Pt nanomotors were designed to label primary antibodies IgG (nanomotor-label) for the "on-the-fly" binding of the immune-protein. The core shell Au@Ag nanocubes (Au@Ag NCs) were used as labels of secondary antibodies (Au@Ag NCs-Ab2) to amplify electrochemical signal related to antigen concentration derived from the oxidation of Ag. The self-propelled nanomotors autonomously move in the solution to cruise and capture IgG and Au@Ag NCs-Ab2, resulting in the self-assembly of sandwich immune-complex. Finally, the immune-complex with magnetism can be transferred and modified on the electrode for the detection of IgG via differential pulse voltammetry. The self-propelled motion of the nanomotor-label obviates common procedures for the self-assembly of sandwich immunosensors to achieve satisfactory analysis results. With advantages of automation and miniaturization, the strategy based on self-propelled nanomotor-labels explores an effective method for the simple and sensitive detection of immune-protein in biosensing.

Rapid synthesis of self-propelled tubular micromotors for "ON-OFF" fluorescent detection of explosives.

We report a rapid strategy to construct self-propelled functional tubular micromotors. Based on the established strategy, magnetic covalent-organic-framework-functionalized micromotors were fabricated to implement sensing of explosives in water. Such micromotors can complete fluorescent "On-Off" detection of trace explosive 2,4,6-trinitrophenol within 10 min.

Dual-stimuli-responsive CuS-based micromotors for efficient photo-Fenton degradation of antibiotics.

Antibiotics as emerging pollutants in water pose great risks to human health. Due to their persistence in the environment, advanced oxidation processes (AOPs) have been proposed for the degradation of antibiotics. Therefore, developing efficient catalysts for AOPs becomes critical for the removal of antibiotics. Herein, we develop self-propelled CuS-based micromotors (CuS@Fe3O4/Pt) as active heterogenous catalysts for efficient photo-Fenton degradation of antibiotics. Combining the merits of conventional heterogenous and homogenous catalysts, the prepared micromotors are easy to recycle and free of secondary pollution risks, while demonstrating high degradation efficiency due to self-induced intensification of mass transfer via autonomous motion and microbubble generation. The H2O2 in the Fenton reagents can serve as the fuel for the micromotors to drive their self-propulsion by bubbles generated from catalytic decomposition of H2O2 by the platinum layer. The dual-stimuli-responsiveness of the micromotors to magnetic field and light irradiation allows multi-modes of propulsion and guidance in different systems. The efficient photothermal effect of CuS enables the micromotors to achieve collective phototactic motion toward light, whereas magnetic responsiveness facilitates the recovery and collection of the micromotors. The synergistic effect of CuS and Fe3O4 NPs in H2O2 under visible light irradiation generates a large amount of OH· and ·O2- to effectively degrade tetracycline within several minutes. With these advantages, the dual-stimuli-responsive CuS-based micromotors provide a new strategy for enhanced degradation of antibiotics in water purification applications.

A sandwich-type electrochemical immunosensor based on Au@Pd nanodendrite functionalized MoO2 nanosheet for highly sensitive detection of HBsAg.

In this work, a sandwich-type electrochemical immunosensor was fabricated to the effective detection of hepatitis B surface antigen (HBsAg). The designed electrochemical immunosensor was based on Au core and Pd shell nanodendrites loaded on amino functionalized molybdenum dioxide nanosheets (Au@Pd NDS/NH2-MoO2 NSs) as the secondary antibody (Ab2) label and silver nanoparticles were loaded by electrodeposited (D-Ag NPs) on the surface of electrode as the platform. Because of the synergistic effect and abundant catalytic activity sites provided by surface dendrite structure, Au@Pd NDs were more effective than single gold and palladium nanoparticles in catalytic reduction of hydrogen peroxide (H2O2). MoO2 had the good catalytic capacity for reduction of H2O2 and favourable electrical conductivity. Hence, the obtained Au@Pd NDS/NH2-MoO2 NSs were more effective than Au@Pd NDs and NH2-MoO2 NSs in catalytic reduction of hydrogen peroxide attribute to a synergistic effect. Also, Ag NPs with admirable electrical conductivity and biocompatibility were used as sensing platforms and primary antibodies (Ab1) carriers, which can accelerate the electron transfer and improve the sensitivity of the immunosensor. Here, the proposed electrochemical immunosensor offered a wide linear interval from 10 fg mL-1 to 100 ng mL-1 and the lower limit of detection of 3.3 fg mL-1 (S/N = 3) for detection of HBsAg under optimal experimental conditions. Furthermore, the accuracy of the actual serum sample analysis was satisfactory, which showed that the electrochemical immunosensor possessed a good application prospect in clinical detection.

LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1.

BACKGROUND: Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet. METHODS: RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified. RESULTS: LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression. CONCLUSIONS: LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.

Electrochemical Immunosensors for Sensitive Detection of Neuron-Specific Enolase Based on Small-Size Trimetallic Au@Pd

Medically, neuron-specific enolase (NSE) as a specific tumor marker has become an important indicator to diagnose small-cell lung carcinoma. In this study, a sandwich-type electrochemical immunosensor was designed to determine NSE sensitively. Au nanoparticle (Au NP)-embedded zinc-based metal-organic frameworks (Au@MOFs) were prepared as the substrate materials to modify the electrode and immobilize the primary antibody (Ab1). The Au@MOFs with the free amino groups on the MOF surface could effectively increase the immobilization amount of Ab1 through covalent linkage. Simultaneously, the embedding of Au NPs improved the conductivity of MOFs and accelerated interface electron transfer. Sub-30 nm trimetallic Au@Pd^Pt nanocubes (Au@Pd^Pt NCs) loaded onto ultrathin MnO2 nanosheets (MnO2 UNs/Au@Pd^Pt NCs) acted as the labels of secondary antibodies. The small-size Au@Pd^Pt NCs enhanced atomic utilization efficiency and offered more catalytic active sites. The MnO2 UNs with high external surface areas could improve the dispersion of Au@Pd^Pt NCs. The MnO2 UNs/Au@Pd^Pt NCs could catalyze the H2O2 reduction and promote the oxidation of hydroquinone to quinone effectively because of their synergistic effect; thus, the generated quinone achieved amplification of the highly reductive peak current. Furthermore, under the optimal conditions, the immunosensor exhibited a low detection limit (4.17 fg/mL) and broad linear range (10 fg/mL to 100 ng/mL). The results were satisfactory for NSE detection in human serum samples, implying that the presented method had great application potential in clinical bioanalysis.

The preparation of hollow AgPt@Pt core-shell nanoparticles loaded on polypyrrole nanosheet modified electrode and its application in immunosensor.

The designed synthesis of efficient materials can significantly enhance the performance of electrochemical immunoassay in the detection of diseases, pesticide residues and environmental pollutants. The hollow AgPt@Pt core-shell nanoparticles (AgPt@Pt HNs) have exhibited high catalytic efficiency to the hydrogen peroxide (H2O2) reduction for its high mass activity from their hollow structure. Their limitation of instability can be overcome by loading on polypyrrole nanosheet (PPy NS). Besides, PPy NS exhibits good conductivity, and there exists environmentally-friendly method for its synthetic. Thus, AgPt@Pt HNs loaded on PPy NS (AgPt@Pt HNs/PPy NS) exhibits high catalytic efficiency to the reduction of H2O2 and good stability. Furthermore, the quick electron transfer of AgPt@Pt HNs/PPy NS modified glassy carbon electrode has been evidenced by the finding that the large constant of apparent electron transfer rate has also enlarged the current signal when the amount of electron is invariant. The modified electrode has fabricated a label-free amperometric immunosensor to detect sensitively prostate-specific antigen (PSA) with H2O2 as the electroactive material. The immunosensor in hollow core-shell nanosheet structure exhibiting good detection performance of PSA shows its promising applications in the clinical diagnosis.

Electrochemical immunosensor based on MoS2 NFs/Au@AgPt YNCs as signal amplification label for sensitive detection of CEA.

Medically, the dynamic change of carcinoembryonic antigen (CEA) concentration has been an important indicator for monitoring and diagnosing tumors. The sensitive and early detection of CEA plays a momentous role in the prevention and diagnosis of cancer and the evaluation of treatment efficiency. In this work, a sensitive sandwich-type electrochemical immunosensor was fabricated for the quantitative detection of CEA. The trimetallic yolk-shell Au@AgPt nanocubes (Au@AgPt YNCs) loaded on amino-functionalized MoS2 nanoflowers (MoS2 NFs/Au@AgPt YNCs) were used as the labels to conjugate with secondary antibodies. The Au@AgPt YNCs with internal space and permeable shell improved catalytic active surface area. The nanosheet-based MoS2 NFs with good catalytic activity were used as carriers to load Au@AgPt YNCs effectively. Due to the biphasic synergistic catalysis, MoS2 NFs/Au@AgPt YNCs catalyzed the reduction of H2O2 effectually to amplify the current signal. Besides, Au triangular nanoprisms (Au TNPs) were used as substrate material to increase the effective contact areas with the surface of electrode and accelerate the interface electron transfer. Under the optimal conditions, a broad linear range from 10 fg mL-1 to 100 ng mL-1 with low detection limit of 3.09 fg mL-1 (S/N = 3) for detecting CEA was obtained. Moreover, the detection results of the human serum samples were satisfactory, indicating the fabricated immunosensor had potential application values in the early clinical analysis.

A sandwich-type electrochemical immunosensor based on RhPt NDs/NH2-GS and Au NPs/PPy NS for quantitative detection hepatitis B surface antigen.

In this work, a sandwich-type electrochemical immunosensor was fabricated to quantitatively detect hepatitis B surface antigen (HBsAg). The immunosensor was based on Rh core and Pt shell nanodendrites loaded onto amino group functionalized graphene nanosheet (RhPt NDs/NH2-GS) as label and gold nanoparticles loaded onto polypyrrole nanosheet (Au NPs/PPy NS) as platform. RhPt NDs with abundant catalytic active sites because of the branched core-shell structure, RhPt NDs/NH2-GS as the label displayed high catalytic activity, amplifying the current signal of the immunosensor. Additionally, Au NPs/PPy NS enhanced the electron transfer and provided a good microenvironment to immobilize antibodies effectively, thus improving the sensitivity of the immunosensor. Based on above advantages, the immunosensor emerged a linear concentration ranging from 0.0005 to 10 ng/mL, a low detection limit of 166 fg/mL for HBsAg (S/N = 3) and good stability, selectivity, reproducibility. Furthermore, the satisfactory accuracy in analysis of actual serum samples implied the immunosensor had promising prospect in clinical analysis applications.

A sandwich-type amperometric immunosensor fabricated by Au@Pd NDs/Fe2+-CS/PPy NTs and Au NPs/NH2-GS to detect CEA sensitively via two detection methods.

The quantitative detection of carcinoembryonic antigen (CEA) is significant to assess tumor status and therapeutic efficiency. In this study, a sandwich-type amperometric immunosensor for CEA detection sensitively was fabricated by novel signal amplification system. The signal amplification system was formed by gold nanoparticles loaded on amino functionalized graphene sheet (Au NPs/NH2-GS) and gold@palladium nanodendrites loaded on ferrous-chitosan functionalized polypyrrole nanotubes (Au@Pd NDs/Fe2+-CS/PPy NTs). Au NPs/NH2-GS as platform enhanced the electron transfer proven by apparent electron transfer rate constant. Au@Pd NDs/Fe2+-CS/PPy NTs nanocomposite as label appeared high catalytic activity to hydrogen peroxide reduction. Thus, the immunosensor showed wide linear concentration range (50 fg/mL to 50 ng/mL) and low detection limit of 17 fg/mL via amperometric i-t curve (i-t). Significantly, the nanocomposite can act as electroactive substance, which provided a good method to detect CEA without additional electroactive substance via square wave voltammetry (SWV). An overlapping linear concentration range (500 fg/mL to 5.0 ng/mL) was obtained compared i-t with SWV. The good reliability was verified mutually by i-t and SWV in actual sample analysis under overlapping linear concentration range. The detection method of without additional electroactive substance has vast potential for future development, due to simple testing condition.