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1.
Anal Chem ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32223184

RESUMO

Efficient DNA mutation-detection methods are required for diagnosis, personalized therapy development, and prognosis assessment for diseases such as cancer. To address this issue, we proposed a straightforward approach by combin-ing active plasmonic nanostructures, surface enhanced Raman spectroscopy (SERS), and polymerase chain reaction (PCR), with a statistical tool to identify and classify BRAF wild type (WT) and V600E mutant genes. The nanostructures provide enhanced sensitivity, while PCR offers the high specificity towards target DNA. A series of positively charged plasmonic nanostructures including gold/silver nanospheres, nanoshells, nanoflowers and nanostars, were synthesized with a one-pot strategy and characterized. By changing the shape of nanostructures, we are able to vary the surface plasmon resonance from 551 nm to 693 nm. The gold/silver nanostar showed the highest SERS activity, which was employed for DNA muta-tion detection. We reproducibly analyzed as few as 100 copies of target DNA sequences using gold/silver nanostars, thus demonstrating the high sensitivity of the direct SERS detection. By means of statistical analysis (principal component anal-ysis-linear discriminant analysis, PCA-LDA), this method was successfully applied to differentiate the WT and V600E mu-tant both from whole genome DNA (gDNA) lysed from cell line and from cell-free DNA (cfDNA) collected from cell culture media. We further proved that this assay is capable of specifically amplifying and accurately classifying a real plasma sample. Thus this direct SERS strategy combined with the active plasmonic nanostructures has the potential for wide appli-cations as an alternative tool for sensitively monitoring and evaluating clinical important nucleotide biomarkers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32216004

RESUMO

The inside walls of a nanopipette tip are decorated by a Pt deposit that is used as an open bipolar electrochemiluminescence (ECL) device to achieve intracellular wireless electroanalysis . The synergetic actions of nanopipette and of bipolar ECL lead to the spatial confinement of the voltage drop at the level of the Pt deposit, which generates ECL emission from luminol. The porous structure of Pt deposit permits the electrochemical transport of intracellular molecules into the nanopipette that is coupled with enzymatic reactions. Thus the intracellular concentrations of hydrogen peroxide or glucose are measured in vivo as well as the intracellular sphingomyelinase activity. In comparison with the classic bipolar ECL, the remarkably low potential applied in our approach is restricted inside the nanopipette and it minimizes the potential bias of the voltage on the cellular activity. Accordingly, this wireless ECL approach provides a new direction for analysis of single living cells.

4.
ACS Sens ; 5(3): 764-771, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32134252

RESUMO

Circulating cancer-derived small extracellular vesicles (EVs) are nanoscale membranous vesicles shed from cancer cells that are released into surrounding body fluids. Small EVs contain biomolecules associated with cancer such as DNA and proteins for cell-to-cell communication. Therefore, small EVs have been regarded as important cancer biomarkers for liquid biopsy-based cancer diagnosis and drug treatment monitoring. However, because of the high heterogeneity and low level of small EVs in body fluids, there is a high demand for sensitive detection and characterization of such vesicles at a molecular level. In this study, we have developed a sensitive and effective approach to simultaneously profile multiple protein biomarkers expressed on cancer-derived small EVs using surface-enhanced Raman spectroscopy (SERS) nanotags in a single test, without complex isolation steps. Rapid and multiplexed phenotypic profiling of small EVs is achieved by mixing specific detection antibody-coated SERS nanotags, filtered conditioned EV-suspended medium (conditioned EVs), and capture antibody (CD63)-conjugated magnetic beads to form a sandwich immunoassay. As a proof-of-concept demonstration, we applied this approach to characterize pancreatic cancer-derived EVs by simultaneously detecting three specific EV surface receptors including Glypican-1, epithelial cell adhesion molecules (EpCAMs), and CD44 variant isoform 6 (CD44V6). The sensitivity of this method was measured down to 2.3 × 106 particles/mL, which is more sensitive and shows higher multiplexing capability than most other reported EV profiling techniques, such as western blot, enzyme-linked immunosorbent assay, and flow cytometry. Furthermore, phenotypic profiling of small EVs from colorectal cancer and bladder cancer cell lines (SW480 and C3) was conducted and compared to those derived from pancreatic cancer (Panc-1), highlighting the significant difference in EV phenotypes for various cancer cell types suspended in both phosphate-buffered saline and plasma. Thus, we believe that this technology enables a comprehensive evaluation of small secreted EV heterogeneity with high sensitivity, offering strong potential for accurate noninvasive cancer diagnosis and monitoring of drug treatment. In addition, this assay provides point-of-care use because of the easy sample preparation and portable nature of the Raman spectrometer.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 233: 118211, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32155579

RESUMO

A series of novel N≡C-CH2-B-F system BODIPY were designed and synthesized by introducing aldehyde and acetonitrile units which gave positive influence to spectroscopic and chemical properties of BODIPY derivatives. The effects of glycine (Gly) on the target products were studied via ultraviolet and visible spectrophotometry (UV-Vis) and photoluminescence (PL) under different conditions of the presence and absence of cations (K+, Ca2+, Zn2+). It was showed that glycine has an intense quenching effect on the compounds in both the presence and absence of ions with a dramatic color change from notable red to light orange owing to the addition of Gly. With regard to cells imaging investigation, the products showed the prominent fluorescence in cholangiocarcinoma cells. The luminescent effect of compounds 1 and 3 entering the cells was significantly stronger than that of compound 2. In addition, pertaining to anticancer properties, two human cancer cell lines (RBE, HCCC-9810) and one normal cell line (L-02) were evaluated for in vitro cytotoxicity. The target compounds, 1-3, exhibited moderate antitumor activity, of which compound 1 was found to be the most potent derivative with IC50 values of 119.31 ± 6.25, 114.73 ± 3.25, and 106.33 ± 5.22 against RBE, HCCC-9810, and L-02 cells, respectively, slightly weaker than the positive control 5-FU.

6.
Rev Sci Instrum ; 91(2): 024709, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113457

RESUMO

In order to increase the security and flexibility of the magnetic field generator, a multi-channel parameters adjustable (MCPA) magnetic field generator is designed and implemented in this paper. The circuit topology of the MCPA magnetic field generator is presented. The working principle of MCPA is analyzed. The pulse current is measured and verified by experiments. The results show that the pulsed current amplitude is adjustable under 1000 A, the adjustment range of the effective pulse width is 0-160 µs, and the adjustment range of the frequency is 1-10 Hz. The magnetic field intensity at 2.5 cm below the scalp of the brain was measured when the three channels were working at the same time. It can be seen that the intensity of the magnetic field in the central area is apparently higher than that in the surrounding. The channels of MCPA can also be chosen flexibly as needed. Therefore, it has a very high application and research value in the field of biological magnetism therapy.

7.
Sci Adv ; 6(9): eaax3223, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32133394

RESUMO

Monitoring targeted therapy in real time for cancer patients could provide vital information about the development of drug resistance and improve therapeutic outcomes. Extracellular vesicles (EVs) have recently emerged as a promising cancer biomarker, and EV phenotyping shows high potential for monitoring treatment responses. Here, we demonstrate the feasibility of monitoring patient treatment responses based on the plasma EV phenotypic evolution using a multiplex EV phenotype analyzer chip (EPAC). EPAC incorporates the nanomixing-enhanced microchip and the multiplex surface-enhanced Raman scattering (SERS) nanotag system for direct EV phenotyping without EV enrichment. In a preclinical model, we observe the EV phenotypic heterogeneity and different phenotypic responses to the treatment. Furthermore, we successfully detect cancer-specific EV phenotypes from melanoma patient plasma. We longitudinally monitor the EV phenotypic evolution of eight melanoma patients receiving targeted therapy and find specific EV profiles involved in the development of drug resistance, reflecting the potential of EV phenotyping for monitoring treatment responses.

8.
Inorg Chem ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32118410

RESUMO

A novel fluorinated biphenyldicarboxylate ligand of 3,3',5,5'-tetrafluorobiphenyl-4,4'-dicarboxylic acid (H2-TFBPDC) and its terbium metal-organic framework, {[Tb2(TFBPDC)3(H2O)]·4.5DMF·0.5H2O}n (denoted as JXNU-6), were synthesized. JXNU-6 exhibits a three-dimensional (3D) framework built from one-dimensional (1D) terbium carboxylate helical chains bridged by TFBPDC2- linkers. The 3D framework of JXNU-6 features 1D fluorine-lined channels. The gas adsorption experiments show that the activated JXNU-6 (JXNU-6a) displays distinct adsorption behavior for propyne (C3H4) and propylene (C3H6) gases. The effective removal of a trace amount of C3H4 from C3H6 was achieved by JXNU-6a under ambient conditions, which is demonstrated by the column-breakthrough experiments. The modeling studies show that the preferential binding sites for C3H4 are the exposed F atoms on the pore surface in 1D channels. The strong C-H···F hydrogen bonds between C3H4 molecules and F atoms of TFBPDC2- ligands dominate the host-guest interactions, which mainly account for the excellent C3H4/C3H6 separation performance of JXNU-6a. This work provides a strategy for specific recognition toward C3H4 over C3H6 through the C-H···F hydrogen bond associated with the fluorinated organic ligand.

9.
Inorg Chem ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045221

RESUMO

Due to the intrinsic coordination preference of the linear uranyl unit, uranyl-organic frameworks (UOFs) are generally prone to exhibiting low-dimensional structures. Reactions of uranyl nitrate with biphenyl-3,3'-disulfonyl-4,4'-dicarboxylic acid dipotassium salt (K2H2BPDSDC) under different conditions led to three UOFs, namely, {(Me2NH2)[K2(UO2)3(µ3-O)(µ3-OH)2(µ2-OH)(BPDSDC)(H2O)3]·4DMF}n (1), {[K2(UO2)(µ3-O)(BPDSDC)0.5(H2O)2]}n (2), and {(Me2NH2)2.5[K1.5(UO2)(BPDSDC)1.5(H2O)3]}n (3). Compounds 1 and 2 contain one-dimensional (1D) ribbon structures formed from UO22+ units bridged by µ3-O atoms and carboxylate groups. The 1D ribbons in 1 are linked by K+ atoms to form a two-dimensional (2D) layer, which is further pillared by the biphenyl units to give a three-dimensional (3D) framework. For 2, the oxygen atoms of UO22+ units in each 1D ribbon bridge the K+ atoms to form four -[K-O-K]n- infinite chains located above and below the ribbon. The 1D ribbons in 2 are bridged by sulfonate groups to generate a 3D substructure featuring 1D channels occupied by biphenyl moieties. In 3, each mononuclear [(UO2)(COO)3] unit is bridged by three K+ atoms to form a 3D substructure featuring 1D small left-handed and large righted helical channels occluded by biphenyl moieties. Compound 2 exhibits an excellent proton conductivity with the highest conductivity of 1.07 × 10-3 S cm-1. The inner walls of 1D channels of 2 are full of the hydrophilic sulfonate groups, which boost enrichment of the guest water molecules, thus resulting in a high proton conductivity. Finally, temperature dependence of fluorescent studies showed that compounds 1 and 2 display the characteristic uranyl emissions. This work presents the elegant examples of the rarely explored 3D UOFs and expands the potentials of UOFs.

10.
Trials ; 21(1): 226, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32102687

RESUMO

BACKGROUND: Pelvic organ prolapse (POP) is a common health problem and has significant negative effects on a woman's quality of life. The transvaginal mesh procedure is a durable reconstructive surgery, but the mesh kits are expensive for underdeveloped countries. Our previous case-series study showed that the use of self-cut mesh had a good success rate (91.8% at 1-year follow-up) and low complication rate. This trial is designed to compare a self-cut titanium-coated polypropylene mesh procedure with a mesh kit for the treatment of symptomatic stage III-IV anterior or apical prolapse in terms of efficacy, safety and cost-effectiveness. METHODS: The trial is a randomized controlled multicenter non-inferiority trial. The primary outcome measure is the composite success rate at 1-year follow-up. The secondary outcomes are anatomic outcomes of each vaginal segment (anterior, posterior and apical) using the POP-Q score, subjective improvement of quality of life according to questionnaires, intraoperative parameters, complications and costs. Analysis will be performed according to the intention-to-treat principle. Based on a comparable success rate of 90% and 10% as the margin (ß = 0.2 and one-sided α = 0.025), about 312 patients in total from 11 centers will be recruited including 10% dropout. The aims of the research are to demonstrate whether the self-cut mesh procedure is non-inferior to the mesh-kit procedure and to investigate the performance of titanium-coated mesh for vaginal prolapse repair. DISCUSSION: This multicenter non-inferiority trial will evaluate whether the efficacy and safety of self-cut mesh is non-inferior to mesh kits in women with severe symptomatic stage III-IV anterior or apical prolapse. If we are able to show that the self-cut mesh procedure is non-inferior to the mesh-kit procedure in success rates, then the self-cut mesh procedure may be more cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03283124. Registered on 17 January 2018.

11.
Phytomedicine ; 68: 153187, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32097779

RESUMO

BACKGROUND: P53 is the most frequently mutated gene in most tumour types, and the mutant p53 protein accumulates at high levels in tumours to promote tumour development and progression. Thus, targeting mutant p53 for degradation is one of the therapeutic strategies used to manage tumours that depend on mutant p53 for survival. Buxus alkaloids are traditionally used in the treatment of cardiovascular diseases. We found that triterpenoid alkaloids extracted from Buxus sinica found in the Yunnan Province exhibit anticancer activity by depleting mutant p53 levels in colon cancer cells. PURPOSE: To explore the anticancer mechanism of action of the triterpenoid alkaloid KBA01 compound by targeting mutant p53 degradation. STUDY DESIGN AND METHODS: Different mutant p53 cell lines were used to evaluate the anticancer activity of KBA01. MTT assay, colony formation assay and cell cycle analysis were performed to examine the effect of KBA01 on cancer cell proliferation. Western blotting and qPCR were used to investigate effects of depleting mutant p53, and a ubiquitination assay was used to determine mutant p53 ubiquitin levels after cells were treated with the compound. Co-IP and small interfering RNA assays were used to explore the effects of KBA01 on the interaction of Hsp90 with mutant p53. RESULTS: The triterpenoid alkaloid KBA01 can induce G2/M cell cycle arrest and the apoptosis of HT29 colon cancer cells. KBA01 decreases the stability of DNA contact mutant p53 proteins through the proteasomal pathway with minimal effects on p53 mutant protein conformation. Moreover, KBA01 enhances the interaction of mutant p53 with Hsp70, CHIP and MDM2, and knocking down CHIP and MDM2 stabilizes mutant p53 levels in KBA01-treated cells. In addition, KBA01 disrupts the HSF1-mutant p53-Hsp90 complex and releases mutant p53 to enable its MDM2- and CHIP-mediated degradation. CONCLUSION: Our study reveals that KBA01 depletes mutant p53 protein in a chaperone-assisted ubiquitin/proteasome degradation pathway in cancer cells, providing insights into potential strategies to target mutant p53 tumours.

12.
Analyst ; 145(7): 2789-2794, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32101179

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be one of the important hospital-acquired pathogens. MRSA is also commonly associated with hospital-acquired infections and mortality. Quantitative and precise detection of MRSA is essential for rapid diagnosis and subsequent effective disease management strategies. We herein developed a highly specific method for rapid MRSA detection that combines surface-enhanced Raman spectroscopy (SERS) nanotags and polymerase chain reaction (PCR). SERS provided the sensitivity and spectral multiplexing capability while PCR provided the specificity required for the assay. The method was tested by the simultaneous detection of two MRSA specific genes (mecA and femA) amplified from genomic DNA isolated from clinical specimens. Magnetic isolation and rapid duplex detection were performed to obtain a detectable signal down to 104 input copies within 80 min. This demonstrated the potential of the SERS-PCR based approach for the accurate identification of MRSA at an early-diagnosis stage. This study also provides an alternative approach to the existing methods for detecting clinical targets without compromising sensitivity and selectivity, and with minimal handling steps. We thus believe that this approach will find a broad application in clinical applications.

13.
Nanoscale ; 12(3): 1948-1957, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31907500

RESUMO

Iron detection is one of the critical markers to diagnose multiple blood-related disorders that correspond to various biological dysfunctions. The currently available anemia detection approach can be used only for pre-treated blood samples that interfere with the actual iron level in blood. Real-time detection approaches with higher sensitivity and specificity are certainly needed to cope with the commercial level clinical analyses. Herein, we presented a novel strategy to determine the blood iron that can be easily practiced at commercial levels. The blend of well-known iron-cyanide chemistry with nanotechnology is advantageous with ultrahigh sensitivity in whole blood analysis without any pre-treatments. This approach is a combined detection system of the conventional assay (UV-visible spectroscopy) with surface-enhanced Raman scattering (SERS). Organic cyanide modified silver nanoparticles (cAgNPs) can selectively respond to Fe3+ ions and Hb protein with a detection limit of 10 fM and 0.46 µg mL-1, respectively, without being affected by matrix interfering species in the complex biological fluid. We confirmed the clinical potential of our new cAgNPs by assessing iron-status in multiple anemia patients and normal controls. Our SERS-based iron quantitation approach is highly affordable for bulk-samples, cheap, quick, flexible, and useful for real-time clinical assays. Such a method for metal-chelation has extendable features of therapeutics molecular tracking within more complex living systems at cellular levels.

14.
Heart Lung ; 49(1): 66-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31376922

RESUMO

BACKGROUND: Atrial fibrillation (AF) burden might link to increased risk of systemic embolism. Current scoring systems for evaluating stroke risks such as CHA2DS2-VASc do not incorporate AF burden partly because of the difficulty to assess these data. Patients with dual-chamber pacemakers implanted have opportunities to acquire incidence and duration of AF. OBJECTIVES: We aimed to evaluate the AF burden and its association with thromboembolism in patients with dual-chamber pacemakers. METHODS: This retrospective cohort study enrolled patients who underwent dual-chamber pacemaker implantation at our center between October 2003 and May 2017. We excluded patients with prior thromboembolism or receiving anticoagulants. The incidence and duration of pacemaker-detected AF were compared between patients with and without thromboembolic outcomes. Propensity score matching (1:1) was conducted based on clinical characteristics. Multivariate regressions were performed to determine the predictors of thromboembolic outcomes. Survival free from stroke and thromboembolism was assessed using Kaplan-Meier analysis in groups with different AF burden. RESULTS: Among the 152 patients enrolled (43.4% women; age 73.2 ±â€¯13.3 years), ten experienced thromboembolic events within a median follow-up of 67 months. Patients with thromboembolisms had higher CHA2DS2-VASc scores but not higher AF burden. Higher CHA2DS2-VASc score was associated with increased risk for systemic thromboembolism [hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.07-3.24; P = 0.027). In the propensity score-matched cohort with comparable CHA2DS2-VASc score, patients with thromboembolism had higher AF burden. Pacemaker-detected AF was associated with increased risk for thromboembolism (propensity-adjusted HR, 9.33; 95% CI, 1.19-72.99; P = 0.033). Experiencing AF episodes lasting >6 min was a predictor of significantly higher risk of future stroke or thromboembolism (propensity-adjusted HR, 6.75; 95% CI, 1.30-35.11; P = 0.023). CONCLUSION: In patients with dual-chamber pacemakers and comparable CHA2DS2-VASc score, pacemaker-detected AF burden is associated with elevated risk for thromboembolism. Further research is needed to clarify how pacemaker-detected AF burden could incorporate with CHA2DS2-VASc score variables and help to guide anticoagulation.

15.
J Cell Mol Med ; 24(2): 1750-1759, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31876059

RESUMO

Stomach cancer is the fourth most common cancer worldwide. Identification of novel molecular therapeutic targets and development of novel treatments are critical. Against a panel of gastric carcinoma cell lines, the activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) was investigated. Adopting RT-PCR, Western blot and immunohistochemical techniques, we sought to determine molecular pharmacodynamic (PD) markers of sensitivity and investigate arylhydrocarbon (AhR) receptor-mediated signal transduction activation by 5F 203. Potent (IC50  ≤ 0.09 µmol/L), selective (>250-fold) in vitro antitumour activity was observed in MKN-45 and AGS carcinoma cells. Exposure of MKN-45 cells to 5F 203 triggered cytosolic AhR translocation to nuclei, inducing CYP1A1 (>50-fold) and CYP2W1 (~20-fold) transcription and protein (CYP1A1 and CYP2W1) expression. G2/M arrest and γH2AX expression preceded apoptosis, evidenced by PARP cleavage. In vivo, significant (P < .01) 5F 203 efficacy was observed against MKN-45 and AGS xenografts. In mice-bearing 5F 203-sensitive MKN-45 and 5F 203-insensitive BGC-823 tumours in opposite flanks, CYP1A1, CYP2W1 and γH2AX protein in MKN-45 tumours only following treatment of mice with 5F 203 (5 mg/kg) revealed PD biomarkers of sensitivity. 5F 203 evokes potent, selective antitumour activity in vitro and in vivo in human gastric cancer models. It triggers AhR signal transduction, CYP-catalysed bioactivation to electrophilic species causing lethal DNA double-strand breaks exclusively in sensitive cells. 5F 203 represents a novel therapeutic agent with a mechanism of action distinct from current clinical drugs, exploiting novel molecular targets pertinent to gastric tumourigenesis: AhR, CYP1A1 and CYP2W1. PD markers of 5F 203 sensitivity that could guide patient selection have been identified.

16.
J Clin Neurosci ; 71: 217-225, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31883812

RESUMO

The accumulation of α-syn which induce endoplasmic reticulum stress (ERS) and mediate various signaling pathways involved in DA neuronal degeneration, and the apoptosis of dopamine (DA) neurons are pathological markers of Parkinson's disease (PD). High-temperature requirement protein A2 (HtrA2) is synthesized in the endoplasmic reticulum, and the expression level of HtrA2 can be upregulated by drugs or by unfolded proteins. Ucf-101 is a specific inhibitor of HtrA2, and studies have shown that Ucf-101 reduced apoptosis in PC12 cells. Our study showed that PC12 cells treated with 60 µM 6-OHDA for 24 h had significantly decreased cell viability compared to that of controls. A low concentration (2.5 µM) of Ucf-101 decreased the apoptosis rate of the PD cell model, but a high concentration (≥10 µM) increased the apoptosis rate, compared to that of controls. 6-OHDA upregulated the expression of HtrA2, α-syn, CHOP, Grp78 and active caspase-3 and reduced the levels of TH and XIAP. Ucf-101 reduced the level of ERS and apoptosis bothin vivoandin vitro. The ratio of p-GSK3ß (Tyr216 to Ser9) increased in PD rats. However, Ucf-101 down-regulated the activation of GSK3ß and activated the Wnt/ß-catenin pathway that was caused by 6-OHDA. Ucf-101 activated the Wnt/ß-catenin pathway and significantly attenuated 6-OHDA-induced neurotoxicity, which was related to the inhibition of ERS and the reduction of the apoptosis rate of PC12 cells and DA neurons in the midbrain of PD rats. Ucf-101 has certain neuroprotective effects.

17.
Adv Sci (Weinh) ; 6(23): 1900730, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832306

RESUMO

Precision oncology, defined as the use of the molecular understanding of cancer to implement personalized patient treatment, is currently at the heart of revolutionizing oncology practice. Due to the need for repeated molecular tumor analyses in facilitating precision oncology, liquid biopsies, which involve the detection of noninvasive cancer biomarkers in circulation, may be a critical key. Yet, existing liquid biopsy analysis technologies are still undergoing an evolution to address the challenges of analyzing trace quantities of circulating tumor biomarkers reliably and cost effectively. Consequently, the recent emergence of cutting-edge plasmonic nanomaterials represents a paradigm shift in harnessing the unique merits of surface-enhanced Raman scattering (SERS) biosensing platforms for clinical liquid biopsy applications. Herein, an expansive review on the design/synthesis of a new generation of diverse plasmonic nanomaterials, and an updated evaluation of their demonstrated SERS-based uses in liquid biopsies, such as circulating tumor cells, tumor-derived extracellular vesicles, as well as circulating cancer proteins, and tumor nucleic acids is presented. Existing challenges impeding the clinical translation of plasmonic nanomaterials for SERS-based liquid biopsy applications are also identified, and outlooks and insights into advancing this rapidly growing field for practical patient use are provided.

18.
J Mater Chem B ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31872850

RESUMO

Atherosclerosis (AS) is the most common factor causing many cardiovascular and cerebrovascular diseases and has received considerable attention. The occurrence mechanism of AS is uncertain because it is a choronically pathological process that is influenced by multi-aspects, among which cytokines play the key roles in regulating the processes of the immune system. For example, two key cytokines, namely, IL-10 and MCP-1 (chemokine), which are involved in AS progression with varied levels, can be used for AS status monitoring and early diagnosis of AS-associated diseases. Hence, a new paper-based, surface-enhanced Raman spectroscopy (SERS) sensing platform was established for the detection of these two key cytokines. By combining a nanoporous networking membrane as the substrate and SERS nanotags as the probe for signal reading, together with a sandwich design, sensitive and specific identification and quantification of cytokine targets in human serum were achieved with excellent sensing characteristics. The lowest detectable concentration was determined to be 0.1 pg mL-1 for both IL-10 and MCP-1 in human serum. The assay also exhibits high specificity towards target cytokine detection, with low-nonspecific binding and acceptable cross-reactivity in the presence of other structurally similar targets. Finally, the practicability was validated by performing duplex detection in human serum, which further demonstrates the high specificity of the assay for the detection of target cytokines. Taken together, these promising results illustrate that this developed sensing assay is a candidate for clinical multi-target analysis in real environments.

19.
Phys Chem Chem Phys ; 21(45): 25148-25157, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31693019

RESUMO

Alternating copolymers (ACPs) have shown several attractive unique characteristics in solution self-assembly due to their special alternating structure. With the introduction of rod segments, much more complexity and multifunctionality can be achieved in the self-assembly of rod-alt-coil ACPs. Herein, we have performed a simulation study on the self-assembly of rod-alt-coil ACPs in dilute solution through dissipative particle dynamics (DPD) simulations. A morphological phase diagram was constructed as a function of rod and coil length, in which diverse assemblies were found, such as bicontinuous micelles and perforated membranes. Furthermore, the alignment of rod segments in the assemblies has been disclosed in detail. And, we deeply investigated the effects of rod length, coil length and π-π interaction strength on the self-assembly morphologies and rod alignment. With the increase of rod length, a disorder-order transition was observed, and π-π interactions could facilitate the orderly alignment of rods. Besides, our simulation results showed good agreement with available experiments. Furthermore, the unique characteristics in the self-assembly of rod-alt-coil alternating copolymers were discussed; in particular we found that the alternating molecular structures of ACPs could promote the orderly alignment of rod segments. We believe that the current work can provide a solid theoretical foundation for further experimental studies.

20.
Small ; 15(50): e1904689, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31724319

RESUMO

The modernized use of nucleic acid (NA) sequences to drive nanostructure self-assembly has given rise to a new class of designed nanomaterials with controllable plasmonic functionalities for broad surface-enhanced Raman scattering (SERS)-based bioanalysis applications. Herein, dual usage of microRNAs (miRNAs) as both valuable cancer biomarkers and direct self-assembly triggers is identified and capitalized upon for custom-designed plasmonic nanostructures. Through strict NA hybridization of miRNA targets, Au nanospheres selectively self-assemble onto hollowed Au/Ag alloy nanocuboids with ideal interparticle distances (≈2.3 nm) for optimal SERS signaling. The intrinsic material properties of the self-assembled nanostructures further elevate miRNA detection performance via nanozyme catalytic SERS signaling cascades. This enables fM-level miR-107 detection limit within a clinically-relevant range without any molecular target amplification. The miRNA-triggered nanostructure self-assembly approach is further applied in clinical patient samples, and showcases the potential of miR-107 as a non-invasive prostate cancer diagnostic biomarker. The use of miRNA targets to drive nanostructure self-assembly holds great promise as a practical tool for miRNA detection in disease applications.

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