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.

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.

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.

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 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.

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.