Facile bio-fabrication of ZnO@AC nanoparticles from chitosan: Characterization, hydrogen generation, and photocatalytic properties.

In this work, activated carbon-supported zinc oxide nanoparticles (ZnO@AC NPs) were studied using the thermal synthesis method. The activated carbon-supported zinc oxide catalyst was characterized by UV-Vis spectrometry techniques, Fourier Transform Infrared Spectrophotometer (FTIR), Transmissive electron microscopy (TEM), and X-ray diffraction (XRD) methods. XRD characterization measurements showed that the average size of the crystal NPs was 6.89 nm. According to the TEM analysis results, the nanoparticles' average size was 11.411 nm, and the particles had a spherical structure. The catalytic properties of the synthesized material were determined using the sodium borohydride methanolysis reaction. A kinetic study was performed regarding the effects of temperature, catalyst, and substrate concentration on the methanolysis reaction. Reusability experiments showed that the catalyst had excellent catalytic activity (85%), stability, and selectivity. As a result of the kinetic study, activation energy, enthalpy (ΔH), entropy (ΔS), and hydrogen production rate activation parameters were found to be 42.52 kJ/mol, 39.98 kJ/mol, -181.42 J/mol.K, 1257.69 mL/min. g, respectively. Also, the photocatalytic activity of ZnO@AC NPs was analyzed against Rhodamine B (RhB) dye, and the maximum degradation percentage was observed to be 76% at 120 min. This study aimed to develop the ZnO@AC NPs into an efficient photocatalyst to prevent industrial wastewater pollution and as a catalyst for hydrogen synthesis as an alternative energy source.

Surgical Nursing Students' Perception of Feedback in Clinical Education: A Mixed-method Study.

BACKGROUND: Feedback is a critical component of education but may not always be delivered in a useful manner. This study assessed surgical nursing students' perception of the feedback they received on a clinical rotation. METHODS: This is a sequential mixed-method study. The first stage surveyed surgical nursing students in surgical units about the feedback they received. In the second stage, participants' experiences receiving feedback were explored in interviews, and analyzed by a conventional content analysis approach. RESULTS: The majority of nurses found that feedback was not helpful, citing a lack of constructive feedback. Negative feedback was often delivered in a public setting. Comments were frequently based on secondary information rather than direct observation. DISCUSSION: Feedback to nurses on the surgical unit is not perceived by students as constructive. Clinical teachers did not appear to be aware of the educational effect of the feedback on the learning process of students. In addition, the setting for feedback often undermined its effectiveness. Staff development on effective feedback for teachers on the surgical unit is recommended.

Extracellular vesicles from serum samples of mycobacteria patients induced cell death of THP-1 monocyte and PBMC.

BACKGROUND: Extracellular vesicles (EVs) play a key role in cell communication and the pathogenesis of some diseases. EVs may accelerate cell death during the course of mycobacterial infection and are also considered as a new vaccine design, drug delivery, and biomarker candidates. The current study evaluates the effects of EVs from serum samples of mycobacteria-infected patients on THP-1 monocytes and PBMC cells. METHOD: EVs were purified from the serum, then cultured separately with THP-1 monocytes and PBMCs. The cell death was determined through annexin V-FITC and PI staining. GW4869, an EVs inhibitor, was used to determine if EVs released from serum could increase THP-1 monocytes cell death. RESULTS: The cell death was significantly increased in the presence of 10 µg/ml and 5 µg/ml concentrations of the purified EVs (p < 0.05). Minimal cell death was determined in 2.5 µg/ml and 1.2 µg/ml (p < 0.05). Up to 85% of the cells were viable in the presence of the GW4869 inhibitor (p < 0.05). CONCLUSION: Direct infection of the cells with EVs released from mycobacteria-infected patients samples, the multiplicity of infection with the EVs, and virulent or avirulent mycobacteria may change the status of the cell death. The isolated EVs  from serum samples of patients with mycobacterial  infection accelerated cell death, which means that they might   not be considered as an optimal tool for developing drug delivery and vaccine against tuberculosis.

Evaluation of the Effect of Fluvoxamine in Patients With Schizophrenia Under Risperidone Treatment: A Clinical Trial.

PURPOSE/BACKGROUND: The effectiveness of selective-serotonin reuptake inhibitors in the improvement of schizophrenia is a controversial issue. The aim of this study was to evaluate the effect of fluvoxamine on the symptoms of schizophrenia including positive and negative symptoms, cognitive impairment, and quality of life. METHODS/PROCEDURES: This clinical trial was performed on 68 patients with chronic schizophrenia, treated with risperidone at 22 Bahman Hospital of Qazvin, Iran during 2015 to 2016. The patients were randomly divided into control and intervention groups (34 patients per group). The control group was treated with risperidone and biperiden, whereas the intervention group received fluvoxamine, besides risperidone, and biperiden. The participants completed the Wechsler Memory Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms (SANS), and the World Health Organization Quality of Life Scale, and the findings were statistically analyzed at baseline and postintervention (8 and 10 weeks). FINDINGS/RESULTS: The mean ± SD Wechsler Memory Scale scores in the evaluated intervals (baseline, week 8, and week 10), respectively, were 70.58 ± 11.51, 70.76 ± 11.36, and 70.88 ± 11.40 in the control group and 74.76 ± 10.56, 77.76 ± 10.56, and 77.76 ± 10.73 in the intervention group (F = 126.73, P ≤ 0.001). The difference between the groups in terms of SANS and quality of life scores was significant in the specified intervals, SANS (F = 6.36, P = 0.004), and quality of life (F = 15.13, P ≤ 0.001). Nevertheless, no difference was observed in terms of Scale for the Assessment of Positive Symptoms scores (P > 0.05). IMPLICATIONS/CONCLUSIONS: The results indicated that risperidone augmentation with fluvoxamine could significantly improve cognitive impairments and negative symptoms among patients with schizophrenia. Moreover, this augmentation led to higher quality of life among these patients.

Evaluation of in-house polymerase chain reaction assay sensitivity, can it be utilized in limited-resources settings?

BACKGROUND: Polymerase chain reaction (PCR) assay has widely used for the detection of tuberculosis (TB). This study tried to compare in-house PCR with some well-known commercial PCR kits for detection of TB agent. METHODS: Clinical samples obtained from 620 TB suspected patients were analyzed for the diagnosis of Mycobacterium tuberculosis complex (MTC) by in-house PCR. All samples were obtained through pulmonary specimens consisted of 384 sputum, 148 bronchial aspirates and 88 pleural effusions. RESULTS: Considering culture as a golden criterion, in which its diagnostic sensitivity and specificity of PCR assay were 87.7% and 85.6%, respectively. The findings of this study also indicate 22.1% (137/620) of the specimens were detected as MTC by PCR. Both PCR and culture confirmed presence of MTC in 57 of the samples. In comparison to culture, the diagnostic sensitivity of PCR for sputum was 87.5% (42/48), bronchial aspirates 100% (12/12), and 60% (3/5) for pleural effusions. The sensitivity of in-house PCR method is comparable with the sensitivity of Amplicor and Cobas TaqMan for MTC. CONCLUSION: The study illustrates the in-house PCR assay for detection of MTC has high sensitivity and specificity versus approved commercial kits. This could be reliable test in the diagnosis of MTC in resource-limited countries.

Feedback-based learning from viewpoints of surgical nursing students: A mixed-method study.

BACKGROUND: Feedback-based learning (FBL) focuses on guiding the learning process according to educational objectives and the student's needs. This study aimed to investigate surgical nursing students' perceptions and explore their experiences of FBL. METHOD: The present study used a mixed-methods sequential explanatory design that was conducted in the quantitative and qualitative phases. Surgical nursing students participated in the quantitative phase (n = 105). In the first phase, students completed two questionnaires about FBL and clinical feedback. Semi-structured face-to-face interviews were used to collect qualitative data in the second phase. Graneheim and Lundman's inductive approaches were used to analyse the qualitative data. RESULTS: The mean (SD) score for students' perception of FBL was 3.99 ± 0.70. The qualitative results were explored in two themes, "motivational support for improvement" and "unpleasant learning". CONCLUSION: In this study, the positive and negative aspects of FBL were explained. FBL is perceived as a motivational support mechanism to improve students' capabilities during their academic courses and also prepare them for future careers. Conversely, FBL may experience unpleasant learning due to negative feedback and negative emotions.

Extracellular Vesicles from Serum of Mycobacteria Patients Accelerate Expression of Apoptosis miRNAs and Facilitate THP-1 Monocyte Cell Death.

Background: Extracellular vesicles (EVs) may accelerate cell death during the course of infection. Mycobacteria could invade the host's immune system and survive in the host by modulation of miRNAs. MiRNAs' differential expressions can serve as biomarkers. This study evaluates THP-1 monocyte cell death by EVs from serum of patients with mycobacteria and assesses serum-derived exosomal miRNAs to increase or decrease THP-1 monocyte cell death. Materials and Methods: EVs were purified from serum of patients with mycobacteria and cultured with THP-1 monocyte. The cell death was determined via annexin V-FITC and PI staining. The microRNA was isolated from serum-derived EVs of the patients. Expression level of Hsa-miR-20a-5p, Hsa-miR-29a, Hsa-miR-let7e, and Hsa-miR-155 was assessed using qRT-PCR. Results: Cell death was accelerated in 10 and 5 µg/ml concentrations of the EVs (p<0.05). Minimum cell death was seen in 2.5 and 1.2 µg/ml concentrations (p<0.05). In tuberculosis (TB) patients, expression of miR-20a-5p, miR-29a, and miR-let7e were significantly enhanced (p≤0.0001), but miR-155 expression reduced. ROC analysis showed diagnostic biomarkers of miRNAs with an AUC=0.6933 for miR-20, AUC=0.6011 for miR-29a, AUC=0.7322 for miR-let7e, and AUC=0.7456 for miR-155 for active tuberculosis. Expression of miR-let7e, 20a, and 29a in M. avium vs. M. tuberculosis was overexpressed (P≤0.01, P≤0.0001, and P≤0.0001, respectively). Also miRs let7e and 20a expression was accelerated in M. abscessus vs. M. tuberculosis (P≤0.0001 and P≤0.002, respectively). Conclusion: EVs accelerates cell death and may not be ideally considered for drug delivery and vaccine developments. Circulating exosomal microRNA MiR-20, miR-let7e, and miR-155 facilitate development of potential biomarkers of pulmonary tuberculosis and non-tuberculosis.

DNA sequencing validation by PCR-RFLP for evaluating butyrophilin-like 2 rs2076530 polymorphism in Iranian patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a multifactorial immune disorder with an uncertain origin. A single nucleotide polymorphism (G→A, rs2076530) in the butyrophilin-like 2 (BTNL2) gene results in the formation of truncating protein. This study aimed to genotype the predisposition of the BTNL2 rs2076530 polymorphism in Iranian patients with sarcoidosis using the RFLP technique. MATERIALS AND METHODS: In this study, 80 patients with sarcoidosis and 80 healthy individuals were included. The rs2076530 polymorphism of the BTNL2 gene was genotyped using the PCR-RFLP method by AvrII restriction enzyme and confirmed by DNA sequencing (Capillary electrophoresis 3130, ABI). RESULTS: There was a statistically significant difference between proportions of patients with AA (47,5%) and controls (27.5%) (OR=2.38, 95%CI:1.23-4.61, P=0.009). In addition, a significant difference was observed in the frequency of the A allele (62.5%) in sarcoidosis (OR=2.14, 95%CI:1.37-3.35, P=0.001). A Bonferroni correction with P<0.0038 indicates a statistical difference for genotype AA (P=0.009). In an effective model, binary logistic regression analysis indicates a statistical association between AA genotype and sarcoidosis (P=0.018 with 60% prediction). Based on the gene analysis study using DNA sequencing, all of the mentioned mutations were seen via RFLP. CONCLUSION: According to our findings, the BTNL2 rs2076530 A allele in the Iranian population is associated with susceptibility to sarcoidosis. This designed PCR-RFLP method for detecting SNPs is effective as DNA sequencing.

Evaluating Factors Affecting the Time Interval Between Propofol Injection and Induction of Electro-convulsion and Relationship Between These Factors and Duration of Convulsion.

BACKGROUND: Current evidence on the effect of anesthetic-ECT time interval (AETI) is controversial. This study aimed to investigate the factors affecting the time interval between propofol injection and electro-convulsion induction and the relationship between these factors and the duration of convulsion. METHODS: In this study, 102 patients (616 sessions of ECT) were studied. Demographic and clinical data (age, gender, receiving or not receiving medications that affected the seizure threshold, the total number of ECT sessions, clinical severity of admission scores, clinical diagnosis, propofol dose, seizure duration, and AETI) were collected in special forms and analyzed by appropriate statistical methods. RESULTS: Sessions with long-term AETI had longer seizure time than sessions with short-term AETI (33.47 ± 8.46 vs. 28.68 ± 9.74, P value < 0.05). The duration of seizures was significantly longer in the group with long AETI in sessions 1, 2, and 4 than in the other group (P value < 0.05). There was a significant relationship between the duration of seizures and propofol dose, AETI, and receiving drugs effective in the seizure threshold (P value < 0.05). CONCLUSIONS: The results showed that increasing AETI and injecting a lower dose of propofol to induce anesthesia would increase the duration of seizures. Also, taking medications that would affect the seizure threshold reduces the duration of seizures.

Telomere length assessment in blood leukocytes of patients with sarcoidosis.

BACKGROUND: Accelerated aging and telomere shortening have been studied in many chronic diseases such as interstitial pulmonary fibrosis and chronic obstructive pulmonary disease. Different studies have shown that patients with these diseases have shorter telomere lengths than controls; this can be a marker of the progression and outcome of the disease. So far, a few studies have been evaluated the telomere length in sarcoidosis. In this study we determine the telomere length in patients with sarcoidosis and compare it with control subjects. OBJECTIVE: Our aim is to compare telomere length in patients with sarcoidosis and normal population. Methods: We select 58 patients with sarcoidosis who were visited in the sarcoidosis clinic of Masih Daneshvari Hospital. 58 sex and age-matched (with±2 years) healthy control subjects were selected. Telomere length was measured by quantitative real time PCR as described by Cawthon on peripheral blood sample. The telomere repeat copy number (T) to single-gene copy number(S) ratio was calculated using the comparative Ct method. Results: The mean and standard deviation of telomere length in the patient and control group was 0.65 ± 0.05 and 0.72 ± 0.07 respectively. There was a statistically significant difference between the two groups. (P = 0.031). Conclusion: Sarcoidosis is an inflammatory disease that can involve many organs. Like other chronic diseases, aging phenomenon occurs in that; which led to decrease cellular and tissue telomere length. This article demonstrates shorter telomere length in Iranian sarcoidosis patients compared to normal population.

Genotypic Characterization of Vancomycin-Resistant Enterococcus spp. In Tertiary Center, Iran.

BACKGROUND: Enterococci infection rate, mortality and morbidity have been increased in recent decades accompanied by progressive emerging antimicrobial resistance. Vancomycin-resistant enterococci (VRE), important pathogen in hospitalized patients, has distinct antibiotic susceptibility to glycopeptides that varied genetically and can influence in choosing therapeutic agents. In this study, we aimed to determine the patterns of antimicrobial resistance according to the genotypic variations in VREs. METHODS: Enterococci samples were isolated from different clinical specimens followed by antimicrobial susceptibility that was determined by the disk diffusion method during one year 2015-2016. Subsequently, VREs were selected and extraction of total DNA was performed using the QIAmp DNA mini kit. The eight oligonucleotide primer pairs were used to amplify the genes vanA, vanB, vanC1, vanC2, vanC2/3, esp, and hyl. Multiplex polymerase chain reaction (PCR) was performed to identify Van A, Van B, Van C, Van D and clonal complex 17 (CC17). RESULTS: A total of 235 enterococci were isolated, including 121 and 114 Enterococcus faecalis and Enterococcus faecium, respectively. Most of VREs (42% of all enterococci) were E. faecium (91.1% vs. 8.9% E. faecalis). All VREs had Van A; and Van B, Van C and Van D genes were not found in any isolates. The frequency rate of CC17, genetic subset of E. faecium, was 68.3%. CONCLUSION: In conclusion, we can assume that the most frequent genotype of VRE in our country is VAN A and literally, the other genotypes.

Insertion/Deletion Polymorphisms and Serum Angiotensin-converting Enzyme Levels in Iranian Patients with Sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disease of unknown origin with characterization of small granulomas. Angiotensin-converting enzyme (ACE) is a pathophysiologic marker of sarcoidosis. We present the ACE insertion/deletion (I/D) polymorphism in correlation with serum ACE level in Iranian patients with sarcoidosis. METHODS: From Jan 2014 to Jan 2015, 102 Iranian patients who histopathologically diagnosed for sarcoidosis and 192 healthy age and sex-matched controls were recruited. PCR was used for detection of I/D polymorphism in ACE gene. RESULTS: Frequency of II/ID/DD genotype in sarcoidosis disease was 17%, 35.5%, and 47.1%, respectively. The frequency of D allele was 0.65. A significant association between I/D genotypes and mean of sACE level was seen (DD=85.2±22.9, P<0.001). More frequent genotype in sarcoidosis patients was DD (47%), ID genotype (45.9%) was found more in controls. Logistic regression analysis adjusting age and sex showed that ID to II (OR=0.35, 95%CI=0.17-0.73, P=0.005) and DD to II (OR=2.11, 95%CI=0.98-4.54, P=0.05) could be considered as a predictor factor for the disease activity. No significant model for men in sarcoidosis group was seen, while women with II/ID were associated with a reduced risk for the disease. CONCLUSION: Although more regional studies with appropriate statistical scale must be done to provide a better diagnosis and prognostic tool for this disease, this study demonstrates that ID and DD genotype could be predictive factors for sarcoidosis.

Telomere Shortening in Blood Leukocytes of Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not completely reversible by administration of inhaled bronchodilators. Many studies propose that telomere length shortening might have occurred in COPD patients. We aimed to determine the telomere length in COPD patients and compare the results of non-smoking and smoking control subjects. MATERIALS AND METHODS: In our case-control study, 84 clinically stable COPD patients were recruited on admission to Masih Daneshvari Hospital. Eighty-five healthy controls were also selected including 45 non-smokers and 40 smokers admitted for diseases other than COPD. Spirometry was done for all subjects. Telomere length was measured by quantitative real time PCR as described by Cawthon. The telomere repeat copy number (T) to single-gene copy number (S) ratio was calculated using the comparative Ct method. RESULTS: The mean ±SD of age was 64.33±10.04 years in patients and 65.06 ±10.02 years in controls (P=0.693). The mean ±SD of FEV1 was 1.62±0.75 L in patients, 2.84±0.54 L in smoker controls and 2.83±0.56 L in non-smoker controls; significant differences were detected in this regard between cases and controls (P<0.001). T/S ratio was significantly lower in COPD patients (0.61±0.08) than in the control subjects (0.69±0.09) (P<0.001). However, telomere length was shorter in the patients than in controls in each age group (P<0.001). Additionally, there were no statistically significant differences in telomere length between the smoker and non-smoker control subjects. Regarding the correlation between BMI and telomere length, there were no significant differences among the patients and control groups. CONCLUSION: In conclusion, we found that telomere length in COPD patients was shorter than that in smoker and non-smoker controls, irrespective of age, sex, spirometric variables, BMI and history of cigarette smoking.

Qualification study of two genomic DNA extraction methods in different clinical samples.

INTRODUCTION: The purity of genomic DNA (gDNA) extracted from different clinical specimens optimizes sensitivity of polymerase chain reaction (PCR) assays. This study attempted to compare two different DNA extraction techniques namely salting-out and classic phenol-chloroform. MATERIALS AND METHODS: Qualification of two different DNA extraction techniques for 634 clinical specimens highly suspected of having mycobacterial infection was performed. Genomic DNA was extracted from 330 clinical samples using phenol-chloroform and 304 by non-toxic salting-out. Qualification of obtained gDNA was done through amplification of internal controls, ß-actin and ß-globin. RESULTS: ß-actin-positive was detected in 279/330 (84%) and 272/304 (89%) samples by phenol-chloroform technique and salting-out, respectively. PCR inhibitor was found for the gDNA of 13/304 (4%) patient samples were negative by ß-actin and ß-globin tests via salting-out technique in comparison with gDNAs from 27/330 (8.5%) samples extracted by phenol-chloroform procedure. No statistically significant difference was found between phenol-chloroform technique and salting-out for 385 sputum, 29 bronchoalveolar lavage (BAL), 105 gastric washing, and 38 body fluid (P=0.04) samples. This illustrates that both techniques have the same quality for extracting gDNA. CONCLUSION: This study discloses salting-out as a non-toxic DNA extraction procedure with a superior time-efficiency and cost-effectiveness in comparison with phenol-chloroform and it can be routinely used in resource-limited laboratory settings.

Polyvinyl alcohol-cellulose nanofibrils-graphene oxide hybrid organic aerogels.

Hybrid organic aerogels consisting of polyvinyl alcohol (PVA), cellulose nanofibrils (CNFs), and graphene oxide nanosheets (GONSs) were prepared using an environmentally friendly freeze-drying process. The material properties of these fabricated aerogels were measured and analyzed using various characterization techniques including compression testing, scanning electron microscopy, thermogravimetric (TGA) analysis, Brunauer-Emmet-Teller (BET) surface area analysis, and contact angle measurements. These environmentally friendly, biobased hybrid organic aerogels exhibited a series of desirable properties including a high specific compressive strength and compressive failure strain, ultralow density and thermal conductivity, good thermal stability, and moisture resistance, making them potentially useful for a broad range of applications including thermal insulation.

Co-delivery of doxorubicin and siRNA using octreotide-conjugated gold nanorods for targeted neuroendocrine cancer therapy.

A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers.

Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging.

A multifunctional unimolecular micelle made of a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for cancer-targeted drug delivery and non-invasive positron emission tomography (PET) imaging in tumor-bearing mice. The hyperbranched amphiphilic block copolymer, Boltorn(®) H40-poly(L-glutamate-hydrazone-doxorubicin)-b-poly(ethylene glycol) (i.e., H40-P(LG-Hyd-DOX)-b-PEG), was conjugated with cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides (cRGD, for integrin α(v)ß(3) targeting) and macrocyclic chelators (1,4,7-triazacyclononane-N, N', N''-triacetic acid [NOTA], for (64)Cu-labeling and PET imaging) (i.e., H40-P(LG-Hyd-DOX)-b-PEG-OCH(3)/cRGD/NOTA, also referred to as H40-DOX-cRGD). The anti-cancer drug, doxorubicin (DOX) was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms (i.e., PLG) via a pH-labile hydrazone linkage to enable pH-controlled drug release. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. cRGD-conjugated unimolecular micelles (i.e., H40-DOX-cRGD) exhibited a much higher cellular uptake in U87MG human glioblastoma cells due to integrin α(v)ß(3)-mediated endocytosis than non-targeted unimolecular micelles (i.e., H40-DOX), thereby leading to a significantly higher cytotoxicity. In U87MG tumor-bearing mice, H40-DOX-cRGD-(64)Cu also exhibited a much higher level of tumor accumulation than H40-DOX-(64)Cu, measured by non-invasive PET imaging and confirmed by biodistribution studies and ex vivo fluorescence imaging. We believe that unimolecular micelles formed by hyperbranched amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics.

Gold Nanorods Conjugated with Doxorubicin and cRGD for Combined Anticancer Drug Delivery and PET Imaging.

A multifunctional gold nanorod (GNR)-based nanoplatform for targeted anticancer drug delivery and positron emission tomography (PET) imaging of tumors was developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX)) was covalently conjugated onto PEGylated (PEG: polyethylene glycol) GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides, cRGD) and (64)Cu-chelators (i.e., 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA)) were conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Based on flow cytometry analysis, cRGD-conjugated nanocarriers (i.e., GNR-DOX-cRGD) exhibited a higher cellular uptake and cytotoxicity than non-targeted ones (i.e., GNR-DOX) in vitro. However, GNR-DOX-cRGD and GNR-DOX nanocarriers had similar in vivo biodistribution according to in vivo PET imaging and biodistribution studies. Due to the unique optical properties of GNRs, this multifunctional GNR-based nanoplatform can potentially be optimized for combined cancer therapies (chemotherapy and photothermal therapy) and multimodality imaging (PET, optical, X-ray computed tomography (CT), etc.).

cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging.

Multifunctional and water-soluble superparamagnetic iron oxide (SPIO) nanocarriers were developed for targeted drug delivery and positron emission tomography/magnetic resonance imaging (PET/MRI) dual-modality imaging of tumors with integrin α(v)ß3 expression. An anticancer drug was conjugated onto the PEGylated SPIO nanocarriers via pH-sensitive bonds. Tumor-targeting ligands, cyclo(Arg-Gly-Asp-d-Phe-Cys) (c(RGDfC)) peptides, and PET 64Cu chelators, macrocyclic 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA), were conjugated onto the distal ends of the PEG arms. The effectiveness of the SPIO nanocarriers as an MRI contrast agent was evaluated via an in vitro r2 MRI relaxivity measurement. cRGD-conjugated SPIO nanocarriers exhibited a higher level of cellular uptake than cRGD-free ones in vitro. Moreover, cRGD-conjugated SPIO nanocarriers showed a much higher level of tumor accumulation than cRGD-free ones according to non-invasive and quantitative PET imaging, and ex vivo biodistribution studies. Thus, these SPIO nanocarriers demonstrated promising properties for combined targeted anticancer drug delivery and PET/MRI dual-modality imaging of tumors.

Ultrasensitive immunosensor for the detection of cancer biomarker based on graphene sheet.

An ultrasensitive electrochemical immunosensor based on graphene sheet (GS) has been developed. GS was used to immobilize mediator thionine (TH), horseradish peroxidase (HRP) and secondary anti-prostate-specific antigen (PSA) antibody (Ab2) and the resulting nanostructure (GS-TH-HRP-Ab2) was used as the label for the immunosensor. With primary anti-PSA antibody (Ab1) also immobilized onto the GS, the immunosensor displayed a wide range of linear response (0.002-10 ng/mL), low detection limit (1 pg/mL), good reproducibility, selectivity and stability. The good performance of the immunosensor is attributed to the graphene sheet's high surface-to-volume ratio which allows the immobilization of a high-level of Ab1, Ab2, TH and HRP and its good electrical conductivity which can improve the electron transfer among TH, HRP, H2O2 and electrode. The immunosensor was used to detect the PSA contents in serum samples from patients and satisfactory test results were obtained in comparison with the ELISA test results. Thus, graphene-based labels may provide many potential applications for the detection of different cancer biomarkers.