A Rationally Designed CRISPR/Cas12a Assay Using a Multimodal Reporter for Various Readouts.

The CRISPR/Cas systems offer a programmable platform for nucleic acid detection, and CRISPR/Cas-based diagnostics (CRISPR-Dx) have demonstrated the ability to target nucleic acids with greater accuracy and flexibility. However, due to the configuration of the reporter and the underlying labeling mechanism, almost all reported CRISPR-Dx rely on a single-option readout, resulting in limitations in end-point result readouts. This is also associated with high reagent consumption and delays in diagnostic reports due to protocol differences. Herein, we report for the first time a rationally designed Cas12a-based multimodal universal reporter (CAMURE) with improved sensitivity that harnesses a dual-mode reporting system, facilitating options in end-point readouts. Through systematic configurations and optimizations, our novel universal reporter achieved a 10-fold sensitivity enhancement compared to the DETECTR reporter. Our unique and versatile reporter could be paired with various readouts, conveying the same diagnostic results. We applied our novel reporter for the detection of staphylococcal enterotoxin A due to its high implication in staphylococcal food poisoning. Integrated with loop-mediated isothermal amplification, our multimodal reporter achieved 10 CFU/mL sensitivity and excellent specificity using a real-time fluorimeter, in-tube fluorescence, and lateral flow strip readouts. We also propose, using artificially contaminated milk samples, a fast (2-5 min) Triton X-100 DNA extraction approach with a comparable yield to the commercial extraction kit. Our CAMURE could be leveraged to detect all gene-encoding SEs by simply reprogramming the guide RNA and could also be applied to the detection of other infections and disease biomarkers.

Mycotoxins detection: view in the lens of molecularly imprinted polymer and nanoparticles.

Molecularly imprinted polymers (MIPs) are tailor-made functional composites which selectively recognize and bind the target molecule of interest. MIP composites are products of the massively cross-linked polymer matrices, generated via polymerization, with bio-inspired recognition cavities that are morphologically similar in size, shape and spatial patterns to the target conformation. These features have enabled researchers to expand the field of molecular recognition, more specifically for target with peculiar requirements. Nevertheless, MIPs alone are characterized with weak sensitivity. Besides, nanoparticles (NPs) are remarkably sensitive but also suffer from poor selectivity. Intriguingly, the combination of the two results in a highly sensitive and selective MIP composite. For instance, the conjugation of different functional NPs with MIPs can generate new flexible target capture tools, either a dynamic sensor or a novel drug delivery system. In this regard, although the technology is considered an established and feasible approach, it is still perceived as a burgeoning technology for various fields, which makes it unceasingly worthy reviewing. Therefore, in this review, we attempt to give an update on various custom-made biosensors based on MIPs in combination with various NPs for the detection of mycotoxins, the toxic secondary metabolites of fungi. We first summarize the classification, prevalence, and toxicological characteristics of common mycotoxins. Next, we provide an overview of MIP composites and their characterization, and then segment the role of NPs with respect to common types of MIP-based sensors. At last, conclusions and outlook are discussed.

Integrated 16S rDNA sequencing and metabolomics to explore the intestinal changes in children and rats with dental fluorosis.

Dental fluorosis (DF) is a widely prevalent disease caused by excessive fluoride with limited awareness of its underlying pathogenesis. Here, a pilot population study was conducted to explore the pathogenesis of DF from the perspective of intestinal microbiome changes, and verified it in animal experiments combining intestinal microbiome and metabolomics. A total of 23 children were recruited in 2017 in China and divided into DF (n = 9) and control (n = 14) groups (DFG and CG, respectively). The SD rat model was established by drinking water containing sodium fluoride (NaF). Gut microbiome profiles of children and rats were analyzed by16S rDNA V3-V4 sequencing, and the intestinal metabolomics analysis of rats was performed by LC-MS methods. The 16 S rDNA sequencing revealed that the gut microbiome composition was significantly perturbed in children in DFG compared to that in CG. Acidobacteria and Thermi were specifically observed in DFG and CG, respectively. Besides, 15 fecal microbiotas were significantly altered at the genus level in DFG. Furthermore, only the expression of annotated genes for pentose and glucuronate interconversion pathway was significant lower in DFG than that in CG (P = 0.04). Notably, in NaF-treated rats, we also observed the changes of some key components of pentose and glucuronate interconversion pathway at the level of microorganisms and metabolites. Our findings suggested that the occurrence of DF is closely related to the alteration of intestinal microorganisms and metabolites annotated in the pentose and glucuronate interconversion pathway.

In Silico Analysis of Ferroptosis-Related Genes and Its Implication in Drug Prediction against Fluorosis.

Fluorosis is a serious global public health problem. Interestingly, so far, there is no specific drug treatment for the treatment of fluorosis. In this paper, the potential mechanisms of 35 ferroptosis-related genes in U87 glial cells exposed to fluoride were explored by bioinformatics methods. Significantly, these genes are involved in oxidative stress, ferroptosis, and decanoate CoA ligase activity. Ten pivotal genes were found by the Maximal Clique Centrality (MCC) algorithm. Furthermore, according to the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD), 10 possible drugs for fluorosis were predicted and screened, and a drug target ferroptosis-related gene network was constructed. Molecular docking was used to study the interaction between small molecule compounds and target proteins. Molecular dynamics (MD) simulation results show that the structure of the Celestrol-HMOX1 composite is stable and the docking effect is the best. In general, Celastrol and LDN-193189 may target ferroptosis-related genes to alleviate the symptoms of fluorosis, which may be effective candidate drugs for the treatment of fluorosis.

Effect of filament types and loops number on the force degradation of elastomeric chains used for orthodontic treatment: an in-vitro study.

BACKGROUND: In orthodontic treatment, closing spaces, specifically the extraction and scattered spaces of the anterior teeth, requires some auxiliary bias, such as an elastomeric chain. Many factors affect the mechanical properties of elastic chains. In this study, we investigated the relationship of the filament type, the number of loops, and the force degradation of elastomeric chains under thermal cycling conditions. METHODS: The orthogonal design included three filament types (i.e., close, medium, and long). Four, five, and six loops of each elastomeric chain were stretched to have an initial force of 250 g in an artificial saliva environment at 37 °C and thermocycling between 5 and 55 °C three times a day. The remaining force of the elastomeric chains was recorded at different time points (4 h, 24 h, 7 days, 14 days, 21 days, and 28 days), and the percentage of the remaining force was calculated. RESULTS: The force decreased significantly in the initial 4 h and degraded mostly within the first 24 h. In addition, the percentage of force degradation increased slightly between 1 and 28 days. CONCLUSIONS: Under the same initial force, the longer the connecting body is, the fewer the number of loops and the greater the force degradation of the elastomeric chain are.

Slit guidance ligand 2 promotes the inflammatory response of periodontitis through activation of the NF-κB signaling pathway.

BACKGROUND AND OBJECTIVES: Periodontitis is a chronic multifactorial inflammatory disease associated with dental plaque biofilms. Slit guidance ligand 2 (SLIT2) has been shown to guide neuronal migration, regulate the inflammatory response and cancer progression. However, the role of SLIT2 in periodontitis is poorly understood. In this study, we investigated the expression of SLIT2 in the gingiva of periodontitis and its role in periodontitis progression. METHODS: Gingiva and gingival crevicular fluid (GCF) were collected from healthy people and periodontitis patients. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to analyze SLIT2 secretion level. Healthy human gingival fibroblasts (hGFs) were isolated and the expression of SLIT2 in lipopolysaccharide (LPS)-treated hGFs was detected. The effect of SLIT2 on inflammation was analyzed using western blot and immunofluorescence. SLIT2 knockdown (KD) and overexpression assays in hGFs were performed to investigate the role of SLIT2 in the LPS-induced inflammatory response. RESULTS: Gingival tissues and GCF of periodontitis patients displayed higher expression of SLIT2. Similarly, SLIT2 was upregulated in hGFs in an inflammatory environment (LPS treatment). In addition, SLIT2 treatment increased the expression of the inflammatory mediators interleukin-6 (IL-6) and IL-8 in hGFs. Mechanistically, SLIT2 stimulated the activation of nuclear factor-κB (NF-κB) signaling, as well as LPS. Lastly, SLIT2 KD impaired LPS-induced IL-6 production in hGFs, while SLIT2 overexpression amplified the inflammatory response. CONCLUSION: SLIT2 may be involved in the aggravation of periodontitis by activating NF-κB signaling in hGFs.

Role of Glycolysis/Gluconeogenesis and HIF-1 Signaling Pathways in Rats with Dental Fluorosis Integrated Proteomics and Metabolomics Analysis.

Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10−3) and glycolysis/gluconeogenesis (FDR = 1.14 × 10−10). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10−7) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.

Ex situ and in situ surface-enhanced Raman spectroscopy for macromolecular profiles of cell nucleus.

Cytobiological methods for cell nucleus-related studies start with the extraction processes of intranuclear components with many cell lysis buffers, following with the structural characterizations and quantitative analysis of the extracted components. In this study, we tried to evaluate the availability and reliability of these extraction-based analytical methods from their spectral features. We implemented an in situ surface-enhanced Raman scattering spectroscopy (SERS) strategy with the help of the nucleus-targeting nanoprobes to investigate the molecular information of nucleus, in comparison with these ex situ methods. This study provides valuable references for choosing an appropriate detection method according to different detection purposes, and also points out the risks of many developing cell-related analytical methods that combine the traditional cytobiological techniques from exogenous interferences during sample preprocesses. Graphical abstract.

Trends of SHBG and ABP levels in male farmers: Influences of environmental fluoride exposure and ESR alpha gene polymorphisms.

A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESRα) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen binding protein (ABP) of male farmers has not been detailed. Here, we conducted a cross-sectional study including 348 male farmers with different fluoride exposure levels from drinking water in Henan province of China to explore effects of fluoride exposure and ESRα genetic variation on serum SHBG and ABP levels. We found serum SHBG levels in male farmers from the high exposure group to be lower than those of the low exposure group. We also found that concentrations of SHBG affected ABP levels. Furthermore, fluoride exposure and single nucleotide polymorphisms at the XbaI and rs3798577 loci of the ESRα gene affected serum ABP levels. Our findings suggest that chronic fluoride exposure from drinking water is associated with alterations of serum SHBG and ABP concentrations in local male farmers and that the effect of fluoride exposure on ABP levels vary depending on ESRα gene polymorphisms.

The peripheral immune cell counts and mouth ulcers: A two-sample Mendelian randomization study.

Objective: This study explored the causal association of peripheral immune cell counts with mouth ulcers (MUs) by two-sample Mendelian Randomization. Design: The counts of 12 circulating immune cell types (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils, CD4+ cells, CD8+ cells, unswitched memory B cells, NK cells, B cells and a derived ratio (CD4+/CD8+)) were determined as the exposure. MUs were the outcome. The analysis was conducted mostly using the inverse-variance weighted (IVW) approach. MR Egger, weighted median, weighted mode and simple mode were used to detect the horizontal pleiotropy. Results: The IVW results for leukocytes and lymphocyte counts were OR = 0.93, 95 % CI = 0.88-0.98, p = 0.0115 and OR = 0.91, 95 % CI: 0.84-0.98, p = 0.0150, respectively. The Wald ratio result for CD4+ cell and CD8+ cell counts were OR = 0.70, 95 % CI: 0.65-0.75, p = 1.05 × 10-20 and OR = 1.25, 95 % CI: 1.19-1.31, p = 9.99 × 10-21, respectively. Conclusions: This study supports a causal effect of peripheral immune cell counts on MUs. Higher leukocyte, lymphocyte and CD4+ cell counts can protect against MUs, but higher CD8+ cell counts enhance the risk of MUs. This finding confirms host immune factors play a crucial role in the aetiology of MUs.

Prevotella intermedia boosts OSCC progression through ISG15 upregulation: a new target for intervention.

PURPOSE: Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects. METHODS: In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups. RESULTS: Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4+ and CD8+ T cells. CONCLUSION: In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.

Proteomics Sequencing Reveals the Role of TGF-ß Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride.

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.

Potential energy profile of colloidal nanoparticles in optical confinement.

An optical bottle method is developed to determine the potential-energy profile of colloidal Rayleigh nanoparticles in an optical trap. The three-dimensional distribution of fluorescent particles in the trap is measured by laser scanning confocal fluorescence microscopy. At sufficiently low concentrations at which interactions between the particles are negligible, the single-particle trapping potential-energy profile is determined from the equilibrium number-density profile by use of the Boltzmann distribution. Fluorescence imaging as well as calculations based on a discrete dipole approximation show that effects due to scattering forces are negligible for polystyrene particles of size less than 10% of the wavelength of the trapping laser, thus justifying the assumption of conservative forces in the equilibrium potential-energy determinations. The new optical bottle method measures the entire two-dimensional trapping-potential profile for an individual nanoparticle without the restriction that only one particle be contained in the trap, thus obviating the need for high laser power.

A new corrosion sensor to determine the start and development of embedded rebar corrosion process at coastal concrete.

The corrosion of reinforcements induced by chloride has resulted to be one of the most frequent causes of their premature damage. Most corrosion sensors were designed to monitor corrosion state in concrete, such as Anode-Ladder-System and Corrowatch System, which are widely used to monitor chloride ingress in marine concrete. However, the monitoring principle of these corrosion sensors is based on the macro-cell test method, so erroneous information may be obtained, especially from concrete under drying or saturated conditions due to concrete resistance taking control in macro-cell corrosion. In this paper, a fast weak polarization method to test corrosion state of reinforcements based on electrochemical polarization dynamics was proposed. Furthermore, a new corrosion sensor for monitoring the corrosion state of concrete cover was developed based on the proposed test method. The sensor was tested in cement mortar, with dry-wet cycle tests to accelerate the chloride ingress rate. The results show that the corrosion sensor can effectively monitor chloride penetration into concrete with little influence of the relative humidity in the concrete. With a reasonable corrosion sensor electrode arrangement, it seems the Ohm-drop effect measured by EIS can be ignored, which makes the tested electrochemical parameters more accurate.

Incidence, associated factors, and outcomes of acute kidney injury following placement of antibiotic bone cement spacers in two-stage exchange for periprosthetic joint infection: a comprehensive study.

Background: Two-stage exchange with placement of antibiotic cement spacer (ACS) is the gold standard for the treatment of chronic periprosthetic joint infection (PJI), but it could cause a high prevalence of acute kidney injury (AKI). However, the results of the current evidence on this topic are too mixed to effectively guide clinical practice. Methods: We retrospectively identified 340 chronic PJI patients who underwent the first-stage exchange with placement of ACS. The Kidney Disease Improving Global Outcomes guideline was used to define postoperative AKI. Multivariate logistic analysis was performed to determine the potential factors associated with AKI. Furthermore, a systematic review and meta-analysis on this topic were conducted to summarize the knowledge in the current literature further. Results: In our cohort, the incidence of AKI following first-stage exchange was 12.1%. Older age (per 10 years, OR= 1.509) and preoperative hypoalbuminemia (OR= 3.593) were independent predictors for postoperative AKI. Eight AKI patients progressed to chronic kidney disease after 90 days. A meta-analysis including a total of 2525 PJI patients showed the incidence of AKI was 16.6%, and AKI requiring acute dialysis was 1.4%. Besides, host characteristics, poor baseline liver function, factors contributing to acute renal blood flow injury, and the use of nephrotoxic drugs may be associated with the development of AKI. However, only a few studies supported an association between antibiotic dose and AKI. Conclusion: AKI occurs in approximately one out of every six PJI patients undergoing first-stage exchange. The pathogenesis of AKI is multifactorial, with hypoalbuminemia could be an overlooked associated factor. Although the need for acute dialysis is uncommon, the fact that some AKI patients will develop CKD still needs to be taken into consideration.

Effects of SNPs in SOD2 and SOD3 interacted with fluoride exposure on the susceptibility of dental fluorosis.

A total of 649 children aged 7-13 years of age were recruited in a cross-sectional study in Tongxu County, China (2017) to assess the effects of interaction between single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 gene and fluoride exposure on dental fluorosis (DF) status. Associations between biomarkers and DF status were evaluated. Logistic regression suggested that the risk of DF in children with rs10370 GG genotype and rs5746136 TT genotype was 1.89-fold and 1.72-fold than that in children with TT/CC genotype, respectively. Increased T-SOD activity was associated with a lower risk of DF (OR = 0.99). The rs2855262*rs10370*UF model was regarded as the optimal interaction model in generalized multifactor dimensionality reduction analyses. Our findings suggested that rs4880 and rs10370 might be useful genetic markers for DF, and there might be interactions among rs10370 in SOD2, rs2855262 in SOD3, and fluoride exposure on DF status.

Seed-mediated synthesis of gold octahedra in high purity and with well-controlled sizes and optical properties.

We report a facile method for the synthesis of uniform Au octahedra with well-controlled sizes and optical properties by seed-mediated growth. Starting from single-crystal seeds of Au spheres with a uniform size, we could reproducibly obtain Au octahedra with a narrow size distribution (<7% in standard deviation) and in high purity (>90%). Moreover, the edge lengths of these Au octahedra could be readily tuned in a controllable fashion from 16 to 77 nm by varying the amount of seeds, the concentration of HAuCl(4) , or both. We have also investigated the effects of water and poly(vinyl pyrrolidone) (PVP) in the system, as well as the reaction temperature, on the evolution of octahedral shape.

A Multifunctional Nanosystem Based on Bacterial Cell-Penetrating Photosensitizer for Fighting Periodontitis Via Combining Photodynamic and Antibiotic Therapies.

Photodynamic therapy (PDT), an emerging approach that involves photosensitizers, light, and molecular oxygen, has shown promise for fighting periodontitis. However, PDT does not always acquire the desired therapeutic outcomes since some photosensitizers have strong hydrophobic properties and are difficult to absorb efficiently by periodontal pathogenic bacteria. Here, a hydrophobic photosensitizer chlorin e6 (Ce6) was hydrophilically modified via conjugation with TAT peptide, a cationic cell-penetrating peptide, to improve its solubility and enhance its bacterial adsorption by promoting its interaction with the negatively charged cell walls and penetration through the cell membranes. The obtained TAT-Ce6 conjugate (TAT-Ce6) was used to prepare self-assembled nanoparticles (NPs) for loading tinidazole (TDZ), a clinically used antibiotic agent, thus hoping to achieve synergistic antiperiodontitis effects through combining PDT and antibiotic therapy. Compared to free Ce6, TAT-Ce6 nanoparticles (TAT-Ce6 NPs) had greatly enhanced adsorption and penetration abilities for periodontal pathogen bacteria and also exhibited significantly increased PDT efficiencies in both periodontal pathogen bacteria and monocyte macrophages. Upon 635 nm laser irradiation, TDZ-loaded TAT-Ce6 (TAT-Ce6/TDZ) NPs exerted remarkable synergistic antiperiodontitis effects of PDT and antibiotic therapy, reflecting in the effective killing of periodontal pathogenic bacteria in vitro and the reduced adsorption of alveolar bone in the Sprague-Dawley rat model of periodontitis. Altogether, this study develops a novel photosensitizer that can be efficiently absorbed by the periodontal pathogenic bacteria and also provides a potent combination strategy of PDT with antibiotic therapy for clinical periodontitis treatment.

Analytical model for optical bistability in nonlinear metal nano-antennae involving Kerr materials.

Optical bistability at nanoscale is a promising way to realize optical switching, a key component of integrated nanophotonic devices. In this work we present an analytical model for optical bistability in a metal nano-antenna involving Kerr nonlinear medium based on detailed analysis of the correlation between the incident and extinction light intensity under surface plasmon resonance (SPR). The model allows one to construct a clear picture on how the threshold, contrast, and other characteristics of optical bistability are influenced by the nonlinear coefficient, incident light intensity, local field enhancement factor, SPR peak width, and other physical parameters of the nano-antenna. It shows that the key towards low threshold power and high contrast optical bistability in the nanosystem is to reduce the SPR peak width. This can be achieved by reducing the absorption of metal materials or introducing gain media into nanosystems.

PEGylated doxorubicin nanoparticles mediated by HN-1 peptide for targeted treatment of oral squamous cell carcinoma.

HN-1, a 12-amino acid peptide, has been reported to possess strong capabilities for targeting and penetrating head and neck squamous cell carcinoma. Here, we designed a simple but effective nanoparticle system for the delivery of doxorubicin (DOX) targeting oral squamous cell carcinoma (OSCC) through the mediation of HN-1. PEGylated DOX (PD) was firstly synthesized by the conjugation of DOX with bis-amino-terminated poly(ethylene glycol) via succinyl linkage, and then PD nanoparticles were prepared by a modified nanoprecipitation method. After that, PD nanoparticles were surface-modified with HN-1 to form HNPD nanoparticles, which had a uniform spherical shape and a small size about 150nm. In human OSCC cells (CAL-27 and SCC-25), HNPD nanoparticles exhibited significantly higher cellular uptakes and cytotoxicities than PD nanoparticles. Furthermore, HNPD nanoparticles showed a certain degree of functional selectivity for CAL-27 and SCC-25 cells as compared to human hepatoma HepG2 cells. In SCC-25 tumor-bearing nude mice, HNPD nanoparticles showed remarkably enhanced tumor-targeting and penetrating efficiencies as compared to PD nanoparticles, and effectively inhibited the tumor growth. In conclusion, our study demonstrated for the first time that HN-1 could be used for mediating the OSCC-targeted delivery of nanoparticles.