拉曼光谱及其在癌症检测中的应用

简述了拉曼光谱的原理、特点及应用,重点介绍了其在在癌症检测和诊断中的应用。     

Surface-Enhanced Raman Scattering from Polyimide Model Compounds on Functionalized Metal Surfaces. Part II: Phthalic Anhydride/meta-Aminothiophenol/Silver

The interphase between a polyimide and a metal substrate was modeled by depositing phthalic anhydride (PA) onto a silver substrate pretreated with meta-aminothiophenol (m-ATP) and then curing in a mixture of acetic anhydride and pyridine or triethylamine. Surface-enhanced Raman scattering (SERS) and reflection-absorption infrared spectroscopy (RAIR) were used to determine the molecular structure of the interphase. It was found that m-ATP was adsorbed dissociatively onto silver substrates through the thiol groups. The tilt angle for m-ATP molecules adsorbed on silver substrates was determined using RAIR to be approximately 39°. However, there was no preferred rotational angle of the adsorbed APDS molecules about the molecular axes. When PA was deposited onto m-ATP pretreated silver substrates, anhydride groups of PA reacted with amino groups of m-ATP to form amic acids. When PA/m-ATP/Ag samples were chemically cured in acetic anhydride and pyridine or triethylamine, isoimide was the predominant product regardless of the use of pyridine or triethylamine as catalyst. These results were different from those obtained from PA/APDS/Au systems in which imide was the major product in the presence of triethylamine. These differences in the relative composition of cured products between two model systems were explained by the effect of substituents attached to APDS and m-ATP benzene rings.     

Diagnostic and Prognostic Role of Extracellular Vesicles in Pancreatic Cancer: Current Evidence and Future Perspectives

Pancreatic cancer is one of the most aggressive tumors, with a dismal prognosis due to poor detection rates at early stages, rapid progression, post-surgical complications, and limited effectiveness of conventional oncologic therapies. There are no consistently reliable biomarkers or imaging modalities to accurately diagnose, classify, and predict the biological behavior of this tumor. Therefore, it is imperative to develop new and improved strategies to detect pancreatic lesions in the early stages of cancerization with greater sensitivity and specificity. Extracellular vesicles, including exosome and microvesicles, are membrane-coated cellular products that are released in the outer environment. All cells produce extracellular vesicles; however, this process is enhanced by inflammation and tumorigenesis. Based on accumulating evidence, extracellular vesicles play a crucial role in pancreatic cancer progression and chemoresistance. Moreover, they may represent potential biomarkers and promising therapy targets. The aim of the present review is to review the current evidence on the role of extracellular vesicles in pancreatic cancer.     

Surface-Enhanced Raman Scattering from Polyimide Model Compounds on Functionalized Metal Surfaces. Part I: Phthalic Anhydride/4-Aminophenyldisul de/Gold

The interphase between a polyimide and a metal substrate was modeled by depositing phthalic anhydride (PA) onto a gold substrate pretreated with 4-aminophenyldisulfide (APDS) and then curing in a mixture of acetic anhydride and pyridine or triethylamine. Surface-enhanced Raman scattering (SERS) and reflection-absorption infrared spectroscopy (RAIR) were used to characterize the model interphases. It was found that APDS was adsorbed dissociatively onto Au substrates through the sulfur atoms. The average tilt angle for APDS molecules adsorbed onto gold substrates was determined, using RAIR, to be approximately 46°. However, there was no preferred rotational angle of the adsorbed APDS molecules about the long molecular axes. When PA was deposited onto APDS-primed Au substrates, anhydride groups of PA reacted with amino groups of APDS to form amic acids. Curing these thin amic acid films in acetic anhydride catalyzed with pyridine produced mainly isoimide species, while curing in the presence of triethylamine gave imide as the major product. The relative amount of isoimide and imide thus depended strongly on the catalyst used in the chemical curing processes.     

Recent Advances in Sandwich SERS Immunosensors for Cancer Detection

Cancer has been one of the most prevalent diseases around the world for many years. Its biomarkers are biological molecules found in the blood or other body fluids of people with cancer diseases. These biomarkers play a crucial role not only in the diagnosis of cancer diseases, but also in risk assessment, selection of treatment methods, and tracking its progress. Therefore, highly sensitive and selective detection and determination of cancer biomarkers are essential from the perspective of oncological diagnostics and planning the treatment process. Immunosensors are special types of biosensors that are based on the recognition of an analyte (antigen) by an antibody. Sandwich immunosensors apply two antibodies: a capture antibody and a detection antibody, with the antigen ‘sandwiched’ between them. Immunosensors’ advantages include not only high sensitivity and selectivity, but also flexible application and reusability. Surface-enhanced Raman spectroscopy, known also as the sensitive and selective method, uses the enhancement of light scattering by analyte molecules adsorbed on a nanostructured surface. The combination of immunosensors with the SERS technique further improves their analytical parameters. In this article, we followed the recent achievements in the field of sandwich SERS immunosensors for cancer biomarker detection and/or determination.     

Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance.     

药物分析中的拉曼光谱技术应用研究

分析了拉曼光谱技术的应用原理及其分类,重点论述了拉曼光谱技术及其在药物分析中的应用发展,为药物分析检测提供技术支持,对提升药物分析能力和分析结果的准确性具有积极的现实意义。     

Design and Synthesis of Novel Raman Reporters for Bioorthogonal SERS Nanoprobes Engineering

Surface-enhanced Raman spectroscopy (SERS) exploiting Raman reporter-labeled nanoparticles (RR@NPs) represents a powerful tool for the improvement of optical bio-assays due to RRs’ narrow peaks, SERS high sensitivity, and potential for multiplexing. In the present work, starting from low-cost and highly available raw materials such as cysteamine and substituted benzoic acids, novel bioorthogonal RRs, characterized by strong signal (10³ counts with FWHM < 15 cm⁻¹) in the biological Raman-silent region (>2000 cm⁻¹), RRs are synthesized by implementing a versatile, modular, and straightforward method with high yields and requiring three steps lasting 18 h, thus overcoming the limitations of current reported procedures. The resulting RRs’ chemical structure has SH-pendant groups exploited for covalent conjugation to high anisotropic gold-NPs. RR@NPs constructs work as SERS nanoprobes demonstrating high colloidal stability while retaining NPs’ physical and vibrational properties, with a limit of detection down to 60 pM. RR@NPs constructs expose carboxylic moieties for further self-assembling of biomolecules (such as antibodies), conferring tagging capabilities to the SERS nanoprobes even in heterogeneous samples, as demonstrated with in vitro experiments by transmembrane proteins tagging in cell cultures. Finally, thanks to their non-overlapping spectra, we envision and preliminary prove the possibility of exploiting RR@NPs constructs simultaneously, aiming at improving current SERS-based multiplexing bioassays.     

Application of Dynamic and Static Light Scattering for Size and Shape Characterization of Small Extracellular Nanoparticles in Plasma and Ascites of Ovarian Cancer Patients

In parallel to medical treatment of ovarian cancer, methods for the early detection of cancer tumors are being sought. In this contribution, the use of non-invasive static (SLS) and dynamic light scattering (DLS) for the characterization of extracellular nanoparticles (ENPs) in body fluids of advanced serous ovarian cancer (OC) and benign gynecological pathology (BP) patients is demonstrated and critically evaluated. Samples of plasma and ascites (OC patients) or plasma, peritoneal fluid, and peritoneal washing (BP patients) were analyzed. The hydrodynamic radius (R_h) and the radius of gyration (R_g) of ENPs were calculated from the angular dependency of LS intensity for two ENP subpopulations. R_h and R_g of the predominant ENP population of OC patients were in the range 20–30 nm (diameter 40–60 nm). In thawed samples, larger particles (R_h mostly above 100 nm) were detected as well. The shape parameter ρ of both particle populations was around 1, which is typical for spherical particles with mass concentrated on the rim, as in vesicles. The R_h and R_g of ENPs in BP patients were larger than in OC patients, with ρ ≈ 1.1–2, implying a more elongated/distorted shape. These results show that SLS and DLS are promising methods for the analysis of morphological features of ENPs and have the potential to discriminate between OC and BP patients. However, further development of the methodology is required.     

Monitoring of polymer content in an emulsion polymerization using spatially resolved spectroscopy in the near infrared region and Raman spectroscopy

The potential of spatially resolved spectroscopy (SRS) for in situ monitoring is evaluated in this work. SRS is based on near-infrared spectroscopy. It is well adapted to heterogeneous systems and collects information about both physical and chemical properties. In this work, the polymer content in emulsion copolymerization is predicted using SRS. The reaction was first carried out in batch mode for particle nucleation followed by semi-continuous monomer addition under starved conditions to allow particle growth. SRS and Raman spectroscopy are compared, and the advantages and disadvantages of both methods are highlighted, revealing that each method has its own benefits. Different operating conditions were varied, including the monomer ratio, the surfactant mass fraction, and the agitation speed. Regression models were developed using partial least square for both techniques.     

Chemical Markers of Human Tendon Health Identified Using Raman Spectroscopy: Potential for In Vivo Assessment

The purpose of this study is to determine whether age-related changes to tendon matrix molecules can be detected using Raman spectroscopy. Raman spectra were collected from human Achilles (n = 8) and tibialis anterior (n = 8) tendon tissue excised from young (17 ± 3 years) and old (72 ± 7 years) age groups. Normalised Raman spectra underwent principal component analysis (PCA), to objectively identify differences between age groups and tendon types. Certain Raman band intensities were correlated with levels of advanced glycation end-product (AGE) collagen crosslinks, quantified using conventional destructive biochemistry techniques. Achilles and tibialis anterior tendons in the old age group demonstrated significantly higher overall Raman intensities and fluorescence levels compared to young tendons. PCA was able to distinguish young and old age groups and different tendon types. Raman intensities differed significantly for several bands, including those previously associated with AGE crosslinks, where a significant positive correlation with biochemical measures was demonstrated. Differences in Raman spectra between old and young tendon tissue and correlation with AGE crosslinks provides the basis for quantifying age-related chemical modifications to tendon matrix molecules in intact tissue. Our results suggest that Raman spectroscopy may provide a powerful tool to assess tendon health and vitality in the future.     

The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine

Ovarian cancer (OvCa) is one of the leading causes of mortality globally with an overall 5-year survival of 47%. The predominant subtype of OvCa is epithelial carcinoma, which can be highly aggressive. This review launches with a summary of the clinical features of OvCa, including staging and current techniques for diagnosis and therapy. Further, the important role of proteases in OvCa progression and dissemination is described. Proteases contribute to tumor angiogenesis, remodeling of extracellular matrix, migration and invasion, major processes in OvCa pathology. Multiple proteases, such as metalloproteinases, trypsin, cathepsin and others, are overexpressed in the tumor tissue. Presence of these catabolic enzymes in OvCa tissue can be exploited for improving early diagnosis and therapeutic options in advanced cases. Nanomedicine, being on the interface of molecular and cellular scales, can be designed to be activated by proteases in the OvCa microenvironment. Various types of protease-enabled nanomedicines are described and the studies that focus on their diagnostic, therapeutic and theranostic potential are reviewed.     

Surface-Enhanced Raman Scattering As an In-Situ Probe of Polyimide/Silver Interphases

The molecular structure of interphases formed by chemically curing the polyamic acid of pyromellitic dianhydride (PMDA) and oxydianiline (ODA) against meta-aminothiophenol (m-ATP)-primed silver substrates was determined using surface-enhanced Raman scattering (SERS) and reflection-absorption infrared spectroscopy (RAIR). It was found that m-ATP was adsorbed dissociatively onto silver substrates through the sulfur atoms. When polyamic acid was deposited onto silver substrates pretreated with m-ATP, acid groups of the polyamic acid combined with amino groups of m-ATP to form ammonium carboxylate salts near the interphase. SERS and RAIR results indicated that the structure of the interphase was significantly different from that of the bulk polymer. Chemical curing of the polyamic acids located in the interphase was suppressed because of the formation of ammonium carboxylate salts. However, the bulk of the polyamic acid films was highly cured to form polyimide. It was also found that more isoimide groups were formed when thin polyamic acid films were chemically cured in acetic anhydride/pyridine solutions than in acetic anhydride/triethylamine solutions.     

FTIR and Raman Spectroscopy of Carbon Nanoparticles in SiO2, ZnO and NiO Matrices

Coatings of carbon nanoparticles dispersed in SiO₂, ZnO and NiO matrices on aluminium substrates have been fabricated by a sol–gel technique. Spectrophotometry was used to determine the solar absorptance and the thermal emittance of the composite coatings with a view to apply these as selective solar absorber surfaces in solar thermal collectors. Cross-sectional high resolution transmission electron microscopy (X-HRTEM) was used to study the fine structure of the samples. Raman spectroscopy was used to estimate the grain size and crystallite size of the carbon clusters of the composite coatings. X-HRTEM studies revealed a nanometric grain size for all types of samples. The C–SiO₂, C–ZnO and C–NiO coatings contained amorphous carbon nanoparticles embedded in nanocrystalline SiO₂, ZnO and NiO matrices, respectively. Selected area electron diffraction (SAED) showed that a small amount of Ni grains of 30 nm diameter also existed in the NiO matrix. The thermal emittances of the samples were 10% for C–SiO₂, 6% for the C–ZnO and 4% for the C–NiO samples. The solar absorptances were 95%, 71% and 84% for the C–SiO₂, C–ZnO and C–NiO samples, respectively. Based on these results, C–NiO samples proved to have the best solar selectivity behaviour followed by the C–ZnO, and last were the C–SiO₂ samples. Raman spectroscopy studies revealed that both the C–ZnO and C–NiO samples have grain sizes for the carbon clusters in the range 55–62 nm and a crystallite size of 6 nm.     

拉曼光谱技术在注射剂快检中的应用研究

从注射剂药品快检的角度出发,运用拉曼光谱技术对注射用头孢拉定、头孢唑林钠、苯巴比妥钠、头孢呋辛钠4种针剂进行快速鉴别、检查。通过与原料药的拉曼光谱进行对比,对特征拉曼信号进行了定性分析,得到了四种样品的拉曼光谱图,为这些药品的鉴定提供了重要的参考数据。本方法操作简便、快速并且对测试样品无损,可成为注射剂快速检测的分析方法。     

Template-Assisted Plasmonic Nanogap Shells for Highly Enhanced Detection of Cancer Biomarkers

We present a template-assisted method for synthesizing nanogap shell structures for biomolecular detections based on surface-enhanced Raman scattering. The interior nanogap-containing a silver shell structure, referred to as a silver nanogap shell (Ag NGS), was fabricated on silver nanoparticles (Ag NPs)-coated silica, by adsorbing small aromatic thiol molecules on the Ag NPs. The Ag NGSs showed a high enhancement factor and good signal uniformity, using 785-nm excitation. We performed in vitro immunoassays using a prostate-specific antigen as a model cancer biomarker with a detection limit of 2 pg/mL. To demonstrate the versatility of Ag NGS nanoprobes, extracellular duplex surface-enhanced Raman scattering (SERS) imaging was also performed to evaluate the co-expression of cancer biomarkers, human epidermal growth factor-2 (HER2) and epidermal growth factor receptor (EGFR), in a non-small cell lung cancer cell line (H522). Developing highly sensitive Ag NGS nanoprobes that enable multiplex biomolecular detection and imaging can open up new possibilities for point-of-care diagnostics and provide appropriate treatment options and prognosis.     

Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies

Molecular diagnostics based on discovery research holds the promise of improving screening methods for prostate cancer (PCa). Furthermore, the congregated information prompts the question whether the urinary extracellular vesicles (uEV) proteome has been thoroughly explored, especially at the proteome level. In fact, most extracellular vesicles (EV) based biomarker studies have mainly targeted plasma or serum. Therefore, in this study, we aim to inquire about possible strategies for urinary biomarker discovery particularly focused on the proteome of urine EVs. Proteomics data deposited in the PRIDE archive were reanalyzed to target identifications of potential PCa markers. Network analysis of the markers proposed by different prostate cancer studies revealed moderate overlap. The recent throughput improvements in mass spectrometry together with the network analysis performed in this study, suggest that a larger standardized cohort may provide potential biomarkers that are able to fully characterize the heterogeneity of PCa. According to our analysis PCa studies based on urinary EV proteome presents higher protein coverage compared to plasma, plasma EV, and voided urine proteome. This together with a direct interaction of the prostate gland and urethra makes uEVs an attractive option for protein biomarker studies. In addition, urinary proteome based PCa studies must also evaluate samples from bladder and renal cancers to assess specificity for PCa.     

拉曼光谱分析技术在汽油调和系统中的应用

针对汽油调和系统的实际需要,研制开发了一套在线拉曼光谱分析系统。该系统应用于实际汽油调和装置,实现了对汽油研究法辛烷值、氧含量及芳烯烃含量等指标的在线分析。通过长时间的运行表明:系统符合设计要求,研究法辛烷值等分析数据能够快速反映调和装置操作条件的变化,可以为工艺装置的操作优化提供准确而重要的检测参数。     

Spatially Resolved Raman Spectroscopy Study of Transformed Zones in Magnesia-Partially-Stabilized Zirconia

Raman vibrational spectroscopy provides an effective phase characterization technique in materials systems containing particle dispersions of the tetragonal and monoclinic polymorphs of zirconia, each of which yields a unique Raman spectrum. An investigation is reported to assess a novel, spatially resolved Raman spectroscopy system in the study of transformed zones surrounding cracks in partially stabilized MgO–ZrO₂ (PSZ). The experimental arrangement uses an imaging (two-dimensional) photomultiplier tube to produce a one-dimensional Raman profile of phase compositions along a slitlike laser beam without translation of either the sample or the laser beam and without scanning the spectrometer. For the present optical configuration, the spatial resolution is estimated to be equivalent to the detector resolution of 28 pm and does not appear to be reduced because of secondary scattering events in the PSZ. Results from phase characterization studies of the size, frontal morphology, and extent of transformation of transformation zones surrounding cracks produced under monotonic and cyclic loading conditions are presented. Particularly large zones are observed in the peak-toughened material, extending 1300 μm ahead of the crack tip with widths of up to 3000 μm. Good agreement is found with similar results determined using optical interference microscopy.     

Raman Spectroscopy of Nanocrystalline Ceria and Zirconia Thin Films

The results of Raman-scattering studies of nanocrystalline CeO₂ and ZrO₂:16% Y (YSZ) thin films are presented. The relationship between the lattice disorder and the form of the Raman spectra is discussed and correlated with the microstructure. It is shown that the Raman line shape results from phonon confinement and spatial correlation effects and yields information about the material nonstoichiometry level.