Multiple valence states of Fe boosting SERS activity of Fe3O4 nanoparticles and enabling effective SERS-MRI bimodal cancer imaging.

Developing novel nanoparticle-based bioprobes utilized in clinical settings with imaging resolutions ranging from cell to tissue levels is a major challenge for tumor diagnosis and treatment. Herein, an optimized strategy for designing a Fe3O4-based bioprobe for dual-modal cancer imaging based on surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI) is introduced. Excellent SERS activity of ultrasmall Fe3O4 nanoparticles (NPs) was discovered, and a 5 × 10-9 M limit of detection for crystal violet molecules was successfully obtained. The high-efficiency interfacial photon-induced charge transfer in Fe3O4 NPs was promoted by multiple electronic energy levels ascribed to the multiple valence states of Fe, which was observed using ultraviolet-visible diffuse reflectance spectroscopy. Density functional theory calculations were utilized to reveal that the narrow band gap and high electron density of states of ultrasmall Fe3O4 NPs significantly boosted the vibronic coupling resonances in the SERS system upon illumination. The subtypes of cancer cells were accurately recognized via high-resolution SERS imaging in vitro using the prepared Fe3O4-based bioprobe with high sensitivity and good specificity. Notably, Fe3O4-based bioprobes simultaneously exhibited T1 -weighted MRI contrast enhancement with an active targeting capability for tumors in vivo. To the best of our knowledge, this is the first report on the use of pure semiconductor-based SERS-MRI dual-modal nanoprobes in tumor imaging in vivo and in vitro, which has been previously realized only using semiconductor-metal complex materials. The non-metallic materials with SERS-MRI dual-modal imaging established in this report are a promising cancer diagnostic platform, which not only showed excellent performance in early tumor diagnosis but also possesses great potential for image-guided tumor treatment.

Discovery of NRG1-VII: the myeloid-derived class of NRG1.

The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined.

Characterizing the Increase in Artificial Intelligence Content Detection in Oncology Scientific Abstracts From 2021 to 2023.

PURPOSE: Artificial intelligence (AI) models can generate scientific abstracts that are difficult to distinguish from the work of human authors. The use of AI in scientific writing and performance of AI detection tools are poorly characterized. METHODS: We extracted text from published scientific abstracts from the ASCO 2021-2023 Annual Meetings. Likelihood of AI content was evaluated by three detectors: GPTZero, Originality.ai, and Sapling. Optimal thresholds for AI content detection were selected using 100 abstracts from before 2020 as negative controls, and 100 produced by OpenAI's GPT-3 and GPT-4 models as positive controls. Logistic regression was used to evaluate the association of predicted AI content with submission year and abstract characteristics, and adjusted odds ratios (aORs) were computed. RESULTS: Fifteen thousand five hundred and fifty-three abstracts met inclusion criteria. Across detectors, abstracts submitted in 2023 were significantly more likely to contain AI content than those in 2021 (aOR range from 1.79 with Originality to 2.37 with Sapling). Online-only publication and lack of clinical trial number were consistently associated with AI content. With optimal thresholds, 99.5%, 96%, and 97% of GPT-3/4-generated abstracts were identified by GPTZero, Originality, and Sapling respectively, and no sampled abstracts from before 2020 were classified as AI generated by the GPTZero and Originality detectors. Correlation between detectors was low to moderate, with Spearman correlation coefficient ranging from 0.14 for Originality and Sapling to 0.47 for Sapling and GPTZero. CONCLUSION: There is an increasing signal of AI content in ASCO abstracts, coinciding with the growing popularity of generative AI models.

SERS Detection of Trace Carcinogenic Aromatic Amines Based on Amorphous MoO3 Monolayers.

Aromatic amines are important commercial chemicals, but their carcinogenicity poses a threat to humans and other organisms, making their rapid quantitative detection increasingly urgent. Here, amorphous MoO3 (a-MoO3) monolayers with localized surface plasmon resonance (LSPR) effect in the visible region are designed for the trace detection of carcinogenic aromatic amine molecules. The hot-electron fast decay component of a-MoO3 decreases from 301 fs to 150 fs after absorption with methyl orange (MO) molecules, indicating the plasmon-induced hot-electron transfer (PIHET) process from a-MoO3 to MO. Therefore, a-MoO3 monolayers present high SERS performance due to the synergistic effect of electromagnetic enhancement (EM) and PIHET, proposing the EM-PIHET synergistic mechanism in a-MoO3. In addition, a-MoO3 possesses higher electron delocalization and electronic state density than crystal MoO3 (c-MoO3), which is conducive to the PIHET. The limit of detection (LOD) for o-aminoazotoluene (o-AAT) is 10-9 M with good uniformity, acid resistance, and thermal stability. In this work, trace detection and identification of various carcinogenic aromatic amines based on a-MoO3 monolayers is realized, which is of great significance for reducing cancer infection rates.

Enhanced Chemoradiotherapy for MRSA-Infected Osteomyelitis Using Immunomodulatory Polymer-Reinforced Nanotherapeutics.

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.

Stimulation of oxalate root exudate in arsenic speciation and fluctuation with phosphate and iron in anoxic mangrove sediment.

Mutual transformations of rhizospheric arsenic (As) in pollution-prone mangrove sediments affected by root exudate oxalate were simulated. This study focuses on the effect of oxalate on As release, mobilization, and phase speciation associated with P and Fe was examined under anoxic conditions in time-dependent changes. Results showed that oxalate addition significantly facilitated As-Fe-P release from As-contaminated mangrove sediments. Sediment As formed the adsorptive and the carbonate-binding fractionations, facilitating the re-adsorption processes. Solution As and As5+ correlated with NaOH-P positively but with NaHCO3-P and HCl-P negatively. Dominant Fe3+ (>84 %) from the amorphous Fe regulated suspension changes and then time-dependent co-precipitation with As and P. Sediment P formed strong complexes with Fe oxides and could be substituted for As via STEM analysis. Oxalate ligand exchange, competitive adsorption of oxalate, and Fe-reduced dissolution are confirmed to involve, allowing for an insight As/P/Fe mobilization and fate in mangrove wetland.

RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway.

The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin ß1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin ß1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin ß1 signaling pathway.

Interference-free SERS nanoprobes for labeling and imaging of MT1-MMP in breast cancer cells.

The expression of membrane type-1 matrix metalloproteinase (MT1-MMP) in cancer cells is critical for understanding the development, invasion and metastasis of cancers. In this study, we devised an interference-free surface-enhanced Raman scattering (SERS) nanoprobe with high selectivity and specificity for MT1-MMP. The nanoprobe was comprised of silver core-silica shell nanoparticle with a Raman reporter tag (4-mercaptobenzonitrile) embedded in the interface. Moreover, the nitrile group in 4-mercaptobenzonitrile shows a unique characteristic peak in the Raman-silent region (1800-2800 cm-1), which eliminates spectral overlapping or background interference in the Raman fingerprint region (500-1800 cm-1). After surface modification with a targeting peptide, the nanoprobe allowed visualization and evaluation of MT1-MMP in breast cancer cells via SERS spectrometry. This interference-free, peptide-functionalized SERS nanoprobe is supposed to be conducive to early diagnosis and invasive assessment of cancer in clinical settings.

Race, ethnicity, and goal-concordance of end-of-life palliative care in pediatric oncology.

BACKGROUND: Racial and ethnic minority children with cancer disproportionately receive intensive care at the end of life (EOL). It is not known whether these differences are goal-concordant or disparities. The authors sought to explore patterns of pediatric palliative care (PPC) and health care utilization in pediatric oncology patients receiving subspecialty palliative care at the end-of-life (last 6 months) and to examine goal-concordance of location of death in a subset of these patients. METHODS: This was a retrospective cohort study of pediatric oncology patients receiving subspecialty palliative care at a single large tertiary care center who died between January 2013 and March 2017. RESULTS: A total of 115 patients including 71 White, non-Hispanic patients and 44 non-White patients (including 12 Black patients and 21 Hispanic patients) were included in the analytic cohort. There were no significant differences in oncologic diagnosis, cause of death, or health care utilization in the last 6 months of life. White and non-White patients had similar PPC utilization including time from initial consult to death and median number of PPC encounters. Non-White patients were significantly more likely to die in the hospital compared to White patients (68% vs 46%, P = .03). Analysis of a subcohort with documented preferences (n = 45) revealed that 91% of White patients and 93% of non-White patients died in their preferred location of death. CONCLUSIONS: Although non-White children with cancer were more likely to die in the hospital, this difference was goal-concordant in our cohort. Subspecialty PPC access may contribute to the achievement of goal-concordant EOL care.

Socioeconomic disparities in survival after high-risk neuroblastoma treatment with modern therapy.

BACKGROUND: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study examined the relationship between socioeconomic status (SES) and overall survival (OS) in children with high-risk neuroblastoma and whether SES-associated disparities have changed over time. PROCEDURE: In this population-based cohort study, children <18 years diagnosed with high-risk neuroblastoma (diagnosis at age ≥12 months with metastatic disease) from 1991 to 2015 were identified through the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Associations of county-level SES variables and OS were tested with univariate Cox proportional hazards regression. For a subcohort diagnosed after 2007, insurance status was examined as an individual-level SES variable. Multivariable regression analyses with treatment era and interaction terms were performed when SES variables reached near-significance (p ≤ .1) in univariate and bivariate modeling with treatment era. RESULTS: Among 1217 children, 2-year OS improved from 53.0 ± 3.4% in 1991-1998 to 76.9 ± 2.9% in 2011-2015 (p < .001). In univariate analyses, children in high-poverty counties (hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.17-2.60, p = .007), and those with Medicaid (HR = 1.40, 95% CI = 1.05-1.86, p = .02) experienced an increased hazard of death. No interactions between treatment era and SES variables were statistically significant in multivariable analyses, indicating that differences in the OS between SES groups did not change over time. CONCLUSIONS: Survival disparities among children with high-risk neuroblastoma have not widened over time, suggesting equitable access to and benefit from therapeutic advances. However, children of low SES experience persistently inferior survival. Interventions to narrow this disparity are paramount.

Building a Harmonized Datamart by Integrating Cross-Institutional Systems of Clinical, Outcome, and Genomic Data: The Pediatric Patient Informatics Platform (PPIP).

PURPOSE: Siloed electronic medical data limits utility and accessibility. At the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, cross-institutional data were inconsistent and difficult to access. To unify data for clinical operations, administration, and research, we developed the Pediatric Patient Informatics Platform (PPIP), an integrated datamart harmonizing multiple source systems across two institutions into a common technology. PATIENTS AND METHODS: Starting in 2009, user requirements were gathered and data sources were prioritized. Project teams, including biostatisticians, database developers, and an external contractor, were formed. Read-access to source systems was established. The 3-layer PPIP architecture was developed: STAGING, a near-exact copy of source data; INTEGRATION, where data were reorganized into domains; and, CONSUMPTION, where data were optimized for rapid retrieval. The diverse systems were integrated into a common IBM Netezza technology. Data filters were defined to accurately capture the Center's patients, and derived data items were created for harmonization across sources. An interactive online query tool, PPIP360, was developed using Microstrategy Analytics. RESULTS: Driven by scientific objectives, the PPIP datamart was created, including 33,674 patients, 2,983 protocols, and 3.6 million patient visits from 14 source databases, 164 source tables, and 2,622 source data items. The PPIP360 has 605 data items and 33 metrics across 11 reports and dashboards. Dana-Farber and Boston Children's established a legal data-sharing agreement. The PPIP has supported hundreds of faculty, staff, and projects, including planning clinical trials and informing strategic planning. CONCLUSION: The PPIP has successfully harmonized and integrated diagnostic, demographic, laboratory, treatment, clinical outcome, pathology, transplant, meta-protocol, and -omics data, for efficient, daily operational and research activities at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, and future external sharing.

Off-label prescribing of targeted anticancer therapy at a large pediatric cancer center.

BACKGROUND: Off-label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. METHODS: We completed a retrospective single-institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off-label prescribing of 108 FDA-approved targeted anticancer drugs in patients < 30 years old treated for cancer from 2007 to 2017. Dosing strategies were adjusted for body size and compared to FDA-approved adult dosing regimen. A composite toxicity endpoint was defined as a patient having unplanned clinic visits, emergency department visits, or unplanned hospital admissions that were at least possibly related to the off-label treatment. RESULTS: The overall prevalence of off-label use of targeted therapies was 9.2% (n = 374 patients). The prevalence increased significantly over the study period (P < .0001). Patients treated off-label were more likely to have neuro-oncology diagnoses compared to patients not treated off-label (46% vs 29%; P < .0001). Of the 108 potential agents, 38 (35%) were used by at least one patient. The median starting dose was below the FDA-approved normalized dose for 44.4% of agents. Fifteen percent of patients had a complete response while receiving off-label therapy, 38% experienced toxicity as defined, and 13% discontinued off-label therapy due to toxicity. CONCLUSIONS: In this real-world evaluation of prescribing at a large pediatric cancer center, off-label prescribing of FDA-approved targeted therapies was common, increasing in prevalence, encompassed a broad sample of targeted agents, and was tolerable. Clinicians commonly start dosing below the equivalent FDA-approved dose.

NO up-regulates migraine-related CGRP via activation of an Akt/GSK-3ß/NF-κB signaling cascade in trigeminal ganglion neurons.

The release of the neuropeptide CGRP from the trigeminal ganglion neurons (TGNs) plays a central role in migraine. Whereas CGRP can activate NO release from ganglionic glial cells, NO in turn enhances CGRP release. However, it remains unclear how NO promotes CGRP release. Here, we report that the NO donor SNAP triggered CGRP release from cultured primary TGNs. This event was associated with GSK-3ß activation and Akt inactivation. Immunofluorescent staining revealed that GSK-3ß primarily located in neurons. Furthermore, GSK-3ß inhibition resulted in a marked reduction in expression of CGRP as well as other migraine-related factors, including substance P, cholecystokinin, and prostaglandin E2. Last, exposure to SNAP also activated NF-κB, while NF-κB inhibition prevented the induction of CGRP by SNAP. Interestingly, this event was blocked by GSK-3ß inhibition, in association with inhibition of NF-κB/p65 expression and nuclear translocation. Together, these findings argue that NO could stimulate TGNs to release of CGRP as well as other migraine-related factors, likely by activating GSK-3ß, providing a novel mechanism underlying a potential feed-forward loop between NO and CGRP in migraine. They also raise a possibility that GSK-3ß might act to trigger migraine through activation of NF-κB, suggesting a link between neuroinflammation and migraine.

Crystal-Amorphous Core-Shell Structure Synergistically Enabling TiO2 Nanoparticles' Remarkable SERS Sensitivity for Cancer Cell Imaging.

Exploring novel surface-enhanced Raman scattering (SERS) active materials with high detection sensitivity, excellent biocompatibility, low biotoxicity, and good spectral stability is urgently required for efficacious cancer cell diagnosis. Herein, black TiO2 nanoparticles (B-TiO2 NPs) with crystal-amorphous core-shell structure are successfully developed. Remarkable SERS activity is derived from the synergistic effect of the promising crystal-amorphous core-shell structure. Abundant excitons can be generated by high-efficiency exciton transitions in the crystal core, a feature that provides sufficient charge source. Significantly, the novel crystal-amorphous heterojunction enables the efficient exciton separation at the crystal-amorphous interface, which can effectively facilitate charge transfer from the crystal core to the amorphous shell and results in exciton enrichment at the amorphous shell. Kelvin probe force microscopy (KPFM) confirms the Fermi level of the amorphous layer shifting to a relatively low position compared to that of the crystal core, allowing efficient photoinduced charge transfer (PICT) between the amorphous shell and probe molecules. The first-principles density functional theory (DFT) calculations further indicate that the amorphous shell structure possesses a narrow band gap and a relatively high electronic density of state (DOS), which can effectively promote vibration coupling with target molecules. Moreover, MCF-7 drug-resistant (MCF-7/ADR) breast cancer cells can be quickly and accurately diagnosed based on the high-sensitivity B-TiO2-based SERS bioprobe. To the best of our knowledge, this is the first time the crystal-amorphous core-shell heterojunction enhancement of the TiO2-molecule PICT process, which widens the application of semiconductor-based SERS platforms in precision diagnosis and treatment of cancer, has been investigated.

Thrombotic Microangiopathy Following Pediatric Autologous Hematopoietic Cell Transplantation: A Report of Significant End-Organ Dysfunction in Eculizumab-Treated Survivors.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a known complication of autologous hematopoietic cell transplantation (aHCT), particularly in children with neuroblastoma. We describe a pediatric single-institution experience of TA-TMA after aHCT. Data were abstracted from the medical record of patients who underwent aHCT between January 1, 2008, and July 1, 2018, at Boston Children's Hospital. TA-TMA was diagnosed using either the International Working Group criteria or the "probable TA-TMA criteria" of Cho et al. Overall, 318 aHCTs were performed in 243 patients. Nine patients (3.7%) were diagnosed with TA-TMA. TA-TMA occurred most frequently in children with neuroblastoma (n = 7; 78%), all of whom were conditioned with carboplatin, etoposide, and melphalan. The median age at aHCT in children who developed TA-TMA was 3 years, 5 months (range, 18 months to 25 years). TMA was diagnosed at a median of 35 days (range, 8 to 106 days) after stem cell infusion. On a retrospective chart review using the same criteria used by the provider, patients met criteria a median of 5 days before the clinical diagnosis (range, 0 to 58 days). Eight patients had renal involvement at presentation, including nephrotic range proteinuria and severe hypertension, requiring from 2 to 6 antihypertensive medications. Two patients presented with multiorgan failure. Six patients were treated with eculizumab a median of 0 days after TA-TMA diagnosis (range, 0 to 11 days). On retrospective review, patients were treated a median of 18 days (range, 0 to 58 days) after meeting criteria for TA-TMA. Before initiation of therapy, 4 of 6 patients checked for serum complement levels had normal values, 1 had elevated CH50 and 1 had elevated sC59-b and CH50. All patients had CH50 levels within the target range (≤3 CAE) after induction therapy. Two patients (33%) had no response to eculizumab and died of multiorgan failure. The other 4 had both a hematologic response with transfusion independence (median, 6.5 weeks; range, 4 to 9 weeks) and renal response, defined as resolution of nephrotic range proteinuria (median, 21 weeks; range, 13 to 25 weeks). Among the eculizumab-treated survivors, 2 patients remained on prolonged eculizumab therapy, and one had recurrence of TA-TMA after discontinuation of eculizumab. All 4 eculizumab treated survivors have persistent organ dysfunction. Three children were treated with supportive care only; 2 died of relapsed cancer, and the third is alive with stage 2 chronic kidney disease. The median duration of follow-up after TA-TMA diagnosis was 2.5 years (range, 9 months to 4 years). The 1-year overall survival was 78% (SE = 14%). However, regardless of treatment, no survivors had complete normalization of function in all organs. Three children with normal serum CH50 and sc5b-9 levels responded to eculizumab. This report highlights the importance of maintaining a high suspicion for TA-TMA after aHCT. Further study is warranted to identify individual risk factors for TMA after aHCT, predict the response to eculizumab, and capture long-term sequelae in survivors.

Molecular Engineering of Conjugated Polymers for Biocompatible Organic Nanoparticles with Highly Efficient Photoacoustic and Photothermal Performance in Cancer Theranostics.

Conjugated polymer nanoparticles (CP NPs) are emerging candidates of "all-in-one" theranostic nanoplatforms with dual photoacoustic imaging (PA) and photothermal therapy (PTT) functions. So far, very limited molecular design guidelines have been developed for achieving CPs with highly efficient PA and PTT performance. Herein, by designing CP1, CP2, and CP3 using different electron acceptors (A) and a planar electron donor (D), we demonstrate how the D-A strength affects their absorption, emission, extinction coefficient, and ultimately PA and PTT performance. The resultant CP NPs have strong PA signals with high photothermal conversion efficiencies and excellent biocompatibility in vitro and in vivo. The CP3 NPs show a high PA signal to background ratio of 47 in U87 tumor-bearing mice, which is superior to other reported PA/PTT theranostic agents. A very small IC50 value of 0.88 µg/mL (CP3 NPs) was obtained for U87 glioma cell ablation under laser irradiation (808 nm, 0.8 W/cm2, 5 min). This study shows that CP NP based theranostic platforms are promising for future personalized nanomedicine.

Refractive index dependent real-time plasmonic nanoprobes on a single silver nanocube for ultrasensitive detection of the lung cancer-associated miRNAs.

We developed a novel method for the real-time monitoring of the delicate change in refractive index (RI) when DNA or RNA hybridize near a DNA-capped silver nanocube (AgNC) surface. This method offers an alternative platform in the quantitative analysis of the trace lung cancer-associated miRNAs in label-free detection.