Accuracy of 14 intraocular lens power calculation formulas in extremely long eyes.

PURPOSE: To compare the accuracy of 14 formulas in calculating intraocular lens (IOL) power in extremely long eyes with axial length (AL) over 30.0 mm. METHODS: In this retrospective study, 211 eyes (211 patients) with ALs > 30.0 mm were successfully treated with cataract surgery without complications. Ocular biometric parameters were obtained from IOLMaster 700. Fourteen formulas were evaluated using the optimized A constants: Barrett Universal II (BUII), Kane, Emmetropia Verifying Optical (EVO) 2.0, PEARL-DGS, T2, SRK/T, Holladay 1, Holladay 2, Haigis and Wang-Koch AL adjusted formulas (SRK/Tmodified-W/K, Holladay 1modified-W/K, Holladay 1NP-modified-W/K, Holladay 2modified-W/K, Holladay 2NP-modified-W/K). The mean prediction error (PE) and standard deviation (SD), mean absolute errors (MAE), median absolute errors (MedAE), and the percentage of prediction errors (PEs) within ± 0.25 D, ± 0.50 D, ± 1.00 D were analyzed. RESULTS: The Kane formula had the smallest MAE (0.43 D) and MedAE (0.34 D). The highest percentage of PE within ± 0.25 D was for EVO 2.0 (37.91%) and the Holladay 1NP-modified-W/K formulas (37.91%). The Kane formula had the highest percentage of PEs in the range of ± 0.50, ± 0.75, ± 1.00, and ± 2.00 D. There was no significant difference in PEs within ± 0.25, ± 0.50 ± 0.75 and ± 1.00 D between BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas (P > .05) by using Cochran's Q test. The Holladay 2modified-W/K formula has the lowest percentage of hyperopic outcomes (29.38%). CONCLUSIONS: The BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas have comparable accuracy for IOL power calculation in eyes with ALs > 30.0 mm.

Deformable Smart DNA Nanomachine for Synergistic Intracellular Cancer-Related miRNAs Imaging and Chemo-Gene Therapy of Drug-Resistant Tumors.

Diagnosis and treatment of tumor especially drug-resistant tumor remains a huge challenge, which requires intelligent nanomedicines with low toxic side effects and high efficacy. Herein, deformable smart DNA nanomachines are developed for synergistic intracellular cancer-related miRNAs imaging and chemo-gene therapy of drug-resistant tumors. The tetrahedral DNA framework (MA-TDNA) with fluorescence quenched component and five antennas is self-assembled first, and then DOX molecules are loaded on the MA-TDNAs followed by linking MUC1-aptamer and Mcl-1 siRNA to the antennas of MA-TDNA, so that the apt-MA-TDNA@DOX-siRNA (DNA nanomachines) is constructed. The DNA nanomachine can respond to two tumor-related miRNAs in vitro and in vivo, which can undergo intelligent miRNA-triggered opening of the framework, resulting in the "turn on" of the fluorescence for sensitively and specifically sensing intracellular miRNAs. Meanwhile, both miRNA-responded rapid release and pH-responded release of DOX are achieved for chemotherapy of tumor. In addition, the gene therapy of the DNA nanomachines is achieved due to the miRNA-specific capture and the RNase H triggered release of Mcl-1 siRNA. The DNA nanomachines intergrading both tumor imaging and chemo-gene therapy in single nanostructures realized efficient tumor-targeted, image-guided, and microenvironment-responsive tumor diagnosis and treatment, which provides a synergetic antitumor effect on drug-resistant tumor.

Colorimetric Detection of Met Dimerization on Live Cells via Smartphone for High-Sensitivity Sensing of the HGF/Met Signaling Pathway.

Membrane protein dimerization regulates numerous cellular biological processes; therefore, highly sensitive and facile detection of membrane protein dimerization are very crucial for clinical diagnosis and biomedical research. Herein, a colorimetric detection of Met dimerization on live cells via smartphone for high-sensitivity sensing of the HGF/Met signaling pathway was developed for the first time. The Met monomers on live cells were recognized by specific ligands (aptamers) first, and the Met dimerizations triggered the proximity-ligation-assisted catalytic hairpin assembly (CHA) reaction to generate large amounts of G-quadruplex (G4) fragments which can further combine hemin to form G4/hemin DNAzymes possessing the horseradish-peroxidase-like catalytic activity for catalyzing the oxidation of ABTS by H2O2 and producing the colorimetric signal (i.e., color change). The colorimetric detection of Met on live cells was then achieved by image acquisition and processing via a smartphone. As a proof-of-principle, the HGF/Met signaling pathway based on Met-Met dimerization was facile monitored, and the human gastric cancer cells MKN-45 with natural Met-Met dimers were sensitively tested and a wide linear working range from 2 to 1000 cells with a low detection limit of 1 cell was obtained. The colorimetric assay possesses a good specificity and high recovery rate of MKN-45 cells spiked in peripheral blood, which indicates that the proposed colorimetric detection of Met dimerization can be used for convenient observation of the HGF/Met signaling pathway and has extensive application prospects in point-of-care testing (POCT) of Met-dimerization-related tumor cells.

Nondestructive separation/enrichment and rolling circle amplification-powered sensitive SERS enumeration of circulating tumor cells via aptamer recognition.

Nondestructive separation/enrichment and reliable detection of extremely rare circulating tumor cells (CTCs) in peripheral blood are of considerable importance in tumor precision diagnosis and treatment, yet this remains a big challenge. Herein, a novel strategy for nondestructive separation/enrichment and ultra-sensitive surface-enhanced Raman scattering (SERS)-based enumeration of CTCs is proposed via aptamer recognition and rolling circle amplification (RCA). In this work the magnetic beads modified with "Aptamer (Apt)-Primer" (AP) probes were utilized to specifically capture CTCs, and then after magnetic separation/enrichment, the RCA-powered SERS counting and benzonase nuclease cleavage-assisted nondestructive release of CTCs were realized, respectively. The AP was assembled by hybridizing the EpCAM-specific aptamer with a primer, and the optimal AP contains 4 mismatched bases. The RCA enhanced SERS signal nearly 4.5-fold, and the SERS strategy has good specificity, uniformity and reproducibility. The proposed SERS detection possesses a good linear relationship with the concentration of MCF-7 cells spiked in PBS with the limit of detection (LOD) of 2 cells/mL, which shows good potential practicality for detecting CTCs in blood with recoveries ranging from 100.56% to 116.78%. Besides, the released CTCs remained good cellular activity with the normal proliferation after re-culture for 48 h and normal growth for at least three generations. The proposed strategy of nondestructive separation/enrichment and SERS-based sensitive enumeration is promising for reliable analysis of EpCAM-positive CTCs in blood, which is expected to provide a powerful tool for analysis of extremely rare circulating tumor cells in complex peripheral blood for liquid biopsy.

A novel cascade signal amplification strategy integrating CRISPR/Cas13a and branched hybridization chain reaction for ultra-sensitive and specific SERS detection of disease-related nucleic acids.

The molecular diagnosis of disease by high-sensitively and specifically detecting extremely trace amounts of nucleic acid biomarkers in biological samples is still a great challenge, and the powerful sensing strategy has become an urgent need for basic researches and clinical applications. Herein, a novel one-pot cascade signal amplification strategy (Cas13a-bHCR) integrating CRISPR/Cas13a system (Cas13a) and branched hybridization chain reaction (bHCR) was proposed for ultra-highly sensitive and specific SERS assay of disease-related nucleic acids on SERS-active silver nanorods sensing chips. The Cas13a-bHCR based SERS assay of gastric cancer-related miRNA-106a (miR-106a) can be achieved within 60 min and output significantly enhanced SERS signal due to the multiple signal amplification, which possesses a good linear calibration curve from 10 aM to 1 nM with the limit of detection (LOD) low to 8.55 aM for detecting gastric cancer-related miR-106a in human serum. The Cas13a-bHCR based SERS sensing also shows good specificity, uniformity, repeatability and reliability, and has good practicability for detection of miR-106a in clinical samples, which can provide a potential powerful tool for SERS detection of disease-related nucleic acids and promise brighter prospects in the field of clinical diagnosis of early disease.

Simultaneous Visualization of Dual Intercellular Signal Transductions via SERS Imaging of Membrane Proteins Dimerization on Single Cells.

The visualization of protein dimerization on live cells is an urgent need and of vital importance for facile monitoring the signal transduction during intercellular communication. Herein, a highly sensitive and specific SERS strategy for simultaneously imaging dual homodimerizations of membrane proteins on single live cells was proposed by networking of AuNPs-based dual-recognition probes (dual-RPs) and SERS tags via proximity ligation-assisted catalytic hairpin assembly (CHA). The dual-RPs were prepared by comodifying hairpin-structured ssDNAs H1-Met and H1-TßRII on 50 nm AuNPs and two SERS tags for membrane proteins Met and TßRII were prepared respectively by labeling their corresponding Raman molecules and hairpin-structured single-stranded DNAs H2-Met or H2-TßRII on 15 nm AuNPs. The membrane proteins were ligated proximally by specific aptamers, and the dimerizations of proteins resulted in the proximity ligation-assisted CHA-based networking of dual-RPs and SERS tags to form 15Au-50Au network nanostructures with significantly enhanced SERS effect. The SERS strategy for visualizing the membrane protein dimerization was established and the good performance on simultaneously SERS imaging dual dimerizations of membrane proteins (i.e., Met-Met and TßRII-TßRII) was confirmed. Furthermore, the membrane protein dimerization-based signaling pathways between cancer cells and stromal cells or stem cells were observed by SERS, which indicates that the proposed SERS strategy is a good method for high-sensitivity monitoring of membrane proteins dimerizations-based multiple intercellular signal transductions in a natural and complex cellular microenvironment.

Sensing gastric cancer exosomes with MoS2-based SERS aptasensor.

Exosomes have been widely used in early cancer diagnosis as promising cancer biomarkers due to their abundant tumor-specific molecular information. In this study, we developed a sensitive and straightforward surface-enhanced Raman scattering (SERS) aptasensor to detect exosomes based on gold nanostars-decorated molybdenum disulfide (MoS2) nanocomposites (MoS2-AuNSs). ROX-labeled aptamers (ROX-Apt) were assembled on MoS2-AuNSs surface as recognition probes that specifically bind with transmembrane protein CD63 (a representative surface marker on exosomes). Thus obvious ROX Raman signals were obtained through the synergistic Raman enhancement effect of AuNSs and MoS2 nanosheet. In presence of exosomes, ROX-Apt is preferentially tethered onto exosomes and released from the surface of nanocomposites, resulting in a decrease of the SERS signal. Expectedly, the as-fabricated SERS aptasensor was capable of detecting exosomes in a wide range from 55 to 5.5 × 105 particles µL-1 with a detection limit of 17 particles µL-1. Moreover, the aptasensor exhibited accepted stability and potential clinical applicability.

Effects of smoking on the retina of patients with dry age-related macular degeneration by optical coherence tomography angiography.

BACKGROUND: The macula of the retina is analysed using optical coherence tomography angiography (OCTA) to provide clinical basis and explain the mechanism of smoking as a risk factor in dry age-related macular degeneration (AMD). METHODS: This cross-sectional study included 49 normal control nonsmokers, 12 normal control smokers, 38 dry AMD nonsmokers and 35 dry AMD smokers. The foveal avascular zone (FAZ), foveal density (FD) in a 300 µm region around FAZ, vessel densities of the superficial (SCP) and deep (DCP) capillary plexuses and central fovea retinal thickness (FRT) were compared using OCTA. The bivariate correlation analysis was used to evaluate the effect of pack-year history on retina-related indices. RESULTS: The vessel densities of whole, foveal and parafoveal of SCP and whole and parafoveal of DCP in the control nonsmoking group were all significantly higher than those in the dry AMD nonsmoking group (all P < 0.05), whereas the whole vessel density of SCP in the normal smoking group was higher than that in the dry AMD smoking group (P = 0.04). The thickness values of the inner and full-layer FRT in the normal nonsmoking group were significantly thicker than those in the dry AMD nonsmoking group (all P < 0.01). The pack-year history was negatively correlated with the parafoveal vessel density of DCP (r = - 0.224, P < 0.01). CONCLUSIONS: FD, SCP, DCP and FRT are sensitive indices for the detection of early and intermediate dry AMD. DCP is a sensitive indicator that reflects the effects of smoking on the retina. Considerable changes are observed in retinal vessels, suggesting that dry AMD may affect the retinal tissue to a certain extent.

Double-Tetrahedral DNA Probe Functionalized Ag Nanorod Biointerface for Effective Capture, Highly Sensitive Detection, and Nondestructive Release of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are indicative of tumorigenesis, metastasis, and recurrence; however, it is still a great challenge to efficiently analyze the extremely rare CTCs in peripheral blood. Herein, a novel nanobiointerface integrating high affinities of arrayed silver nanorods (Ag NRs) and double-tetrahedral DNA (DTDN) probes by a clever strategy is proposed for the efficient capture, highly sensitive detection, and nondestructive release of CTCs. Under the optimal conditions, the DTDN-probe-functionalized Ag NRs nanobiointerface can capture 90.2% of SGC-7901 cells in PBS, and the capture efficiency is 2.8 times and 50 times those of a DTDN-probe-functionalized Ag film and unfunctionalized Ag NRs, respectively, benefiting from the nanorough interface of the Ag NRs array and multivalent recognition of the DTDN probe. In addition, 93.4% of cells was released via Zn2+-assisted DNAzyme cleavage, and the viability of the postreleased CTCs is about 98.0%. The potential practicality of the nanobiointerface for testing CTCs in blood was further characterized by spiking SGC-7901 cells in leukocytes collected from human blood, and the results show that 83.8% capture efficiency, 91.2% release efficiency, and single-cell detection limit were achieved, which indicates that the nanobiointerface has great potential in clinical applications for reliable CTC analyses.

DNA walker-powered ratiometric SERS cytosensor of circulating tumor cells with single-cell sensitivity.

Identification and detection of extreme rare circulating tumor cells (CTCs) in peripheral blood can precisely monitor cancer recurrence and metastasis, however, how to ultra-sensitively and reliably detect CTCs is a big challenge. In this work, a ratiometric surface-enhanced Raman spectroscopy (SERS)-based strategy for ultra-sensitively and nondestructively detecting CTCs was proposed via CTCs-triggered DNA walker-assisted assembly of plasmonic nanostructure networks consisting of Walker probes and SERS tags. The Walker probes were prepared by modifying Fe3O4@SiO2@Au nanoparticles (GMNPs) with ROX-labeled EpCAM aptamer-blocked Zn2+-specific DNAzyme and hairpin-structured single-stranded DNAs H1, and the SERS tags were constructed by co-labelling hairpin-structured single-stranded DNAs H2 and Raman molecules (DTNB) on Au NPs. The aptamers can recognize EpCAM-positive CTCs via the specific binding to EpCAM, so that the activity of DNAzymes is activated with the assistance of Zn2+ to launch the DNA walker to move around for the cleavage of H1 on GMNPs. The residual fragments of H1 on GMNPs can hybridize with H2 on SERS tags and result in the formation of Walker probe-SERS tag network nanostructures (Nw NSs) with rich SERS hot spots. The reliable SERS detection of CTCs is achieved by the stable ratiometric SERS signals of DTNB and ROX generated from the Nw NSs, and a good linear relation between ratiometric SERS signal and MCF-7 cells concentration was obtained with the detection limit low to 1 cell/mL. The recovery rate of MCF-7 cells in peripheral blood is in the range of 94.0%-104.5%, which indicates a good application prospect of the novel ratiometric SERS cytosensor in the clinic detection of EpCAM-positive CTCs.

Intracellular miRNA-Triggered Surface-Enhanced Raman Scattering Imaging and Dual Gene-Silencing Therapy of Cancer Cell.

Development of theranostic nanosystems integrating cascaded surface-enhanced Raman scattering (SERS) imaging and gene silencing therapy for accurate cancer diagnosis and treatment is still a big challenge and rarely reported. Herein, a novel Au nanoparticles (AuNPs)-based theranostic nanosystem containing AuNP-Ys and AuNP-Ds for highly sensitive and specific cancer diagnosis and treatment was proposed for cascaded SERS imaging of intracellular cancer-related miR-106a and miR-106a-triggered DNAzyme-based dual gene-silencing therapy of cancer cells. The AuNP-Ys were prepared by modifying the AuNPs with specially designed Y-motifs, and the AuNP-Ds were obtained by colabeling Raman molecules and dsDNA linkers on AuNPs. When identifying the intracellular cancer-related miRNAs, the Y-motifs and dsDNA linkers undergoes miRNA-triggered ATP-driven conformational transitions and releases the miRNA for recycling, which results in the formation of AuNP network nanostructures to generate significantly enhanced SERS signals for sensitive identification of the cancer cells as well as the amplification and specific activation of DNAzymes to catalyze the Mg2+-assisted cleavage of the Survivin and c-Jun mRNAs for effective dual gene-silencing therapy of cancer cells. The AuNP-based theranostic nanosystem achieves the synergism of target-triggered SERS imaging and DNAzyme-based dual gene-silencing therapy with enhanced specificity, sensitivity, and curative effect, which can be a powerful tool for accurate diagnosis and efficient treatment of cancers.

The exploration of quantum dot-molecular beacon based MoS2 fluorescence probing for myeloma-related Mirnas detection.

Highly sensitive and reliable detection of multiple myeloma remains a major challenge in liquid biopsy. Herein, for the first time, quantum dot-molecular beacon (QD-MB) functionalized MoS2 (QD-MB @MoS2) fluorescent probes were designed for the dual detection of multiple myeloma (MM)-related miRNA-155 and miRNA-150. The results indicate that the two probes can effectively detect miRNA-155 and miRNA-150 simultaneously with satisfactory recovery rates, and the limit of detections (LODs) of miRNA-155 and miRNA-150 in human serum are low to 7.19 fM and 5.84 fM, respectively. These results indicate that our method is the most sensitive detection so far reported and that the designed fluorescent probes with signal amplification strategies can achieve highly sensitive detection of MM-related miRNAs for MM diagnosis.

DNA self-assembled Au nanoparticle clusters on silver nanorod arrays for high-sensitive and multiplex detection of cancer-related biomarkers.

To sensitively detect multiple and cross-species disease-related targets from a single biological sample in a quick and reliable manner is of high importance in accurately diagnosing and monitoring diseases. Herein, a surface-enhanced Raman scattering (SERS) sensor based on a functionalized multiple-armed tetrahedral DNA nanostructure (FMTDN) immobilized silver nanorod (AgNR) array substrate and Au nanoparticle (AuNP) SERS tags is constructed to achieve both multiplex detection and enhanced sensitivity using a sandwich strategy. The sensor can achieve single, dual, and triple biomarker detections of three lung cancer-related nucleic acid and protein biomarkers, i.e., miRNA-21, miRNA-486 and carcinoembryonic antigen (CEA) in human serum. The enhanced SERS signals in multiplex detections are due to the DNA self-assembled AuNP clusters on the silver nanorod array during the assay, and the experimentally obtained relative enhancement factor ratios, 150 for AuNP dimers and 840 for AuNP trimers, qualitatively agree with the numerically calculated local electric field enhancements. The proposed FMTDN-functionalized AgNR SERS sensor is capable of multiplex and cross-species detection of nucleic acid and protein biomarkers with improved sensitivity, which has great potential for the screening and clinical diagnosis of cancer in the early stage.

SPR/SERS dual-mode plasmonic biosensor via catalytic hairpin assembly-induced AuNP network.

Highly sensitive and reliable detection of disease-related nucleic acids is still a big challenge in liquid biopsy because of their homologous sequences and low abundance. Herein, a novel surface plasmon resonance/surface-enhanced Raman scattering (SPR/SERS) dual-mode plasmonic biosensor based on catalytic hairpin assembly (CHA)-induced Au nanoparticle (AuNP) network was proposed for highly sensitive and reliable detection of cancer-related miRNA-652. The biosensor includes capture DNA-functionalized AuNPs (Probe 1), H1 and 4-mercaptobenzoic acid (4-MBA) co-modified AuNPs (Probe 2), and 6-carboxyl-Xrhodamine (ROX)-labeled H2 (fuel strands). The Probe 1-Probe 2 networks were formed via the target-triggered CHA reactions, which resulted in the color change of dark-field microscopy (DFM) images and enhanced SERS effect. The SPR sensing was achieved by extracting the integral optical density of dark-field color in DFM images, and the SERS sensing was realized by the ratiometric SERS signals of ROX and internal standards 4-MBA molecules. After characterizing the feasibility and optimality of the sensing strategy, the good performance of biosensors on sensitivity, specificity and uniformity was approved. The practicability of biosensors was confirmed by detecting miRNA-652 in human serum, and both the SPR and SERS assays showed good linear calibration curves and low limit of detections (LODs) of 42.5 fM and 2.91 fM, respectively, with the recovery in the range of 94.67-111.4%. These two modes show complementary advantages, and the combined SPR/SERS dual-mode can provide more options for detection and double check the results to improve the accuracy and reliability of assays, which holds a great application prospect for cancer-related nucleic acids detection in early disease stage.

Highly Sensitive Detection of miRNA-155 Using Molecular Beacon-Functionalized Monolayer MoS2 Nanosheet Probes with Duplex-Specific Nuclease-Mediated Signal Amplification.

MicroRNA-155 (miRNA-155) as a characteristic myeloma-associated biomarker exhibits significant potential application in the diagnosis of multiple myeloma (MM). In this paper, a novel type of molecular beacon (MB)-functionalized monolayer MoS2 nanosheet probe was proposed as fluorescent probe for high-sensitive assays of miRNA-155that uses a duplexspecificnuclease (DSN) enzyme to amplify the fluorescence signal. The preparation and detection conditions of the fluorescent probes were optimized in some aspects, such as the concentration of MoS2 (0.80 µM) and DSN (0.2 U), and the incubation time of DSN (30 min). The probesexhibited a sensitive fluorescence response to miRNA-155 and the fluorescence signal of the assay was significantly amplified by the cleavage of DSN. The relationship between F/F0 and logC miRNA follows a linear calibration curve, and the limit of detection (LOD) of miRNA-155 in 10% human serum is calculated to be 10.96 fM based on this relationship. The good performance and fluorescence amplification effect of the fluorescent probe were confirmed by studying the recovery of miRNA-155 in 10% human serum, which was ranged from 98.32% to 106.3% with a relative standard deviation of less than 4.14%. Besides, the high expression of miRNA-155 in clinic blood of MM patients was sensitively distinguished from healthy peoples by using the proposed probes. The proposed novel fluorescent probe based on the DSN can be used to detect miRNA-155 in human serum and provide a potential, convenient and reliable tool for diagnosis of MM.

Ultrasensitive SERS detection of nucleic acids via simultaneous amplification of target-triggered enzyme-free recycling and multiple-reporter.

The development of ultrasensitive and specific methods for facile detection of trace nucleic acids is of great significance to human health and safety. In the present work, an ultrasensitive SERS-based strategy for detecting nucleic acids was proposed by integrating the SERS-active AgNRs array with double signal amplifications, i.e. the primary target-triggered enzyme-free amplification recycling and the secondary signal enhancement of multiple-reporter. By comparing two SERS sensing routes, i.e. solid interface recycling (Route A) and solution recycling (Route B), the superior solution recycling was determined first, and then the sensing strategy was optimized by investigating the immobilization time, surface blocking, and number of reporters utilized in the SERS sensing. The experimental results indicate that an ultrasensitive SERS strategy can be achieved via the primary amplification of target-triggered enzyme-free recycling and additional enhancement by the usage of multiple reporters. Under the optimal conditions, the SERS sensing showed good specificity and uniformity, and a linear calibration curve of DNAs in human serum solution, ranging from 1 µM to 1 fM, was obtained with LOD as low as 40.4 aM, and the following recovery rate measurements confirmed that the proposed SERS sensing had good repeatability and reliability, which shows great potential for facile detecting trace DNAs, especially disease-related nucleic acids in the liquid biopsy of early-stage cancer detection.

Gold nanostars for cancer cell-targeted SERS-imaging and NIR light-triggered plasmonic photothermal therapy (PPTT) in the first and second biological windows.

Cancer cell-targeted imaging and efficient therapy are vital for tumor diagnosis and treatments. However, the development of multifunctional plasmonic nanoparticles with high-performance SERS-imaging and NIR light-triggered plasmonic photothermal therapy (PPTT) of cancer cells in both the first (NIR-I) and second (NIR-II) biological windows is still a big challenge. In the present work, gold nanostars which possess a broad NIR absorption band covering the NIR-I and NIR-II windows with good NIR SERS activity and photothermal effects were synthesized by a seed-mediated growth method, using gold chloride (HAuCl4), ascorbic acid (AA) and (1-hexadecyl) trimethylammonium chloride (CTAC) as growth solutions. The gold nanostars were further designed to be multifunctional nanoagents by labeling Raman molecules and then conjugating arginine-glycine-aspartic acid (RGD), which can serve as cancer cell-targeted SERS-imaging tags and photothermal nanoagents in both the NIR-I and NIR-II windows. The investigation of in vitro SERS-mapping and PPTT of the A549 human lung adenocarcinoma cells indicates that the proposed multifunctional gold nanostars have great potential for a wide spectrum of light-mediated applications, such as optical imaging and image-guided phototherapy in both the NIR-I and NIR-II biological windows.

A gold nanoflower-based traceable drug delivery system for intracellular SERS imaging-guided targeted chemo-phototherapy.

Accurate and effective drug delivery in tumor cells significantly improves the curative effect with high drug delivery efficiency, low toxicity and side effects and has become an urgent demand for anticancer therapy. In this paper, a novel traceable and targeted drug delivery nanosystem (i.e. AuNF-nanocarriers) with high drug encapsulation and pH-controlled release was prepared based on gold nanoflowers (AuNFs) for efficient intracellular SERS imaging-guided chemo-phototherapy. SERS-active flower-like gold nanoparticles with large surface area were synthesized first and then modified with Raman and RGD molecules in sequence to prepare bright, traceable and targeted SERS tags of A549 human lung cancer cells. Furthermore, thiolated-PAA (PAA-SH) was synthesized and utilized for the first time to modify the SERS tags with a layer of negative charges for efficient pH-dependent loading and release of the anticancer drug doxorubicin. Based on the A549 human lung cancer cell model, the availability of the proposed AuNF-nanocarriers for efficient intracellular SERS imaging-guided chemo-phototherapy was studied and the results indicate that the AuNF-based drug delivery system exhibited attractive characteristics such as good stability, efficiency and pH-controlled drug loading and release, traceable and targeted delivery, as well as SERS imaging and chemo-phototherapy functions, and shows great potential for powerful SERS-imaging and as a theranostic candidate for precision nanomedicine that could achieve sensitive and accurate tumor detection and therapy.

Combination assay of lung cancer associated serum markers using surface-enhanced Raman spectroscopy.

The development of an ultrasensitive analysis technique for the combination assay of cancer associated markers is an effective method for the early detection of tumor. Herein, we report a highly sensitive and specific SERS-based sandwich immunoassay for the simultaneous detection of two protein markers associated with lung cancer, including carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE). Two bright SERS tags are prepared by surface modifications of flower-like gold nanoparticles with Raman molecules and target-specific antibodies, and SERS-active magnetic nanoparticles labelled with mixed antibodies are used as immune substrates for capturing the targets and further separating the sandwich structured immune complexes from the mixture. Immunoassays for joint detection of CEA and NSE using both buffer and human serum specimens are performed and the assay results indicate that the proposed SERS-based combination assay of the two markers shows good specificity and ultrahigh sensitivity. The limit of detections of CEA and NSE in human serum specimens are 1.48 pg mL-1 and 2.04 pg mL-1, respectively. The proposed SERS immunoassay is expected to be used for multiple-marker assays of any other tumors and to provide a reliable method for the early screening of cancers in clinic.

Distinguishing breast cancer cells using surface-enhanced Raman scattering.

The detection and identification of epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is crucial for the clinic therapy of breast cancer. For the aim of the detection, a novel surface-enhanced Raman scattering (SERS) probe for distinguishing breast cancers at different HER2 statuses is reported in this paper. In such a probe, anti-HER2 antibody-conjugated silver nanoparticles have been synthesized for specific targeting of HER2-positive breast cancer cells. More importantly, different from the previously reported SERS probe for targeting cancer cells, p-mercaptobenzoic acid is utilized as both the Raman reporter and the conjugation agent for attaching antibody molecules, which leads to a much simplified structure. For investigating the ability of such a probe to distinguish breast cancer cells, SKBR3 and MCF7 cells were chosen as two model systems, which are HER2-positive- and HER2-negative-expressing cells, respectively. The experimental results reveal that SKBR3 cells exhibit much stronger SERS signals than MCF7 cells, indicating that the probe could be utilized to distinguish breast cancer cells at different HER2 statuses. This kind of SERS probe holds a potential for a direct detection of living breast cancer cells with the advantages of easy fabrication, high SERS sensitivity, and biocompatibility.