Modeling the instability of CNT tweezers using a continuum model

Carbon nanotube (CNT) tweezers are composed of two parallel cantilever CNTs with a distance in between. In this paper, the static response and instability of CNT-made nano-tweezers is theoretically investigated considering the effects of Coulomb electrostatic force and van der Waals molecular attraction. For this purpose, a nano-scale continuum model is employed to obtain the nonlinear constitutive equation of the nano-tweezers. The Euler-Bernoulli beam theory is applied to model the elastic response of the CNT. The van der Waals attraction is computed from the simplified Lennard-Jones potential. In order to solve the nonlinear constitutive equation of the system, three approaches, e.g. the hemotopy perturbation method (HPM), the Adomian decomposition (AD) and the finite difference method (FDM) are employed. The obtained results are in good agreement with the experimental measurements. As a case study, freestanding CNT tweezers has been investigated and the detachment length and minimum initial gap of the tweezers are determined. Moreover, the effective operation range of the van der Waals attraction that affects the instability behavior of the CNT tweezers is discussed

Precision Localization of Lipid-Based Nanoparticles by Dual-Fluorescent Labeling for Accurate and High-Resolution Imaging in Living Cells

In nanomedicine, lipid-based nanoparticles (NPs) such as liposomes (LPs) have established an important position. Precise delineation of NP interaction with cells and detailed characterization of activity are becoming essential, which mainly rely on labeling with lipophilic fluorescent molecules and assuming stable association with NPs. However, because of label separation from NPs in (biological) media, or when processed by cells, fluorescence-based detection of an NP incorporating a single label may not necessarily indicate the actual presence of an NP but may be from the dissociated label, rendering results unreliable. Herein, flow cytometry and confocal microscopy are employed to demonstrate that to verify the localization of LPs in a cell with perfect accuracy, dual-labeling, and contemporaneous detection of both fluorescent signals in one pixel are required. This is combined with size exclusion chromatography (SEC) and mass spectrometry measurements to indicate factors involved in label dissociation, which helps to understand the possible conditions of dissociated label and NP. It is shown that determining label colocalization with, and label dissociation from, dual-labeled NPs are needed to provide accurate spatiotemporal insight into targeting destination (colocalized signals) and disintegration (separated signals) of NPs during intracellular processing and in studying payload delivery with precision in nanomedicine.</p

Relationship between Body Mass Index, Waistto- Hip Ratio, and Serum Lipid Concentrations and Thyroid-Stimulating Hormone in the Euthyroid Adult Population

The aim of this cross-sectional study was to investigate the relationship between body mass index (BMI), waist-to-hip ratio, and lipid parameters and serum thyroid-stimulating hormone (TSH) levels in healthy euthyroid individuals. This cross-sectional study was conducted between June 1st and July 20th, 2013, at Bushehr University of Medical Sciences. One hundred forty euthyroid individuals were divided into 2 groups: a high-TSH group (TSH between 2.0 and 5.5 mIU/L, n=67) and a low-TSH group (TSH between 0.3 and 2.0 mIU/L, n=73). After overnight fast, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TSH, thyroxine (T4), and triiodothyronine (T3) were measured. Height and weight were measured with a stadiometer, and BMI was calculated as weight in kilograms divided by the square of height in meters. Waistto- hip ratio was determined as waist circumference divided by hip circumference. The simple independent t-test and a general linear model were used for statistical analysis. All statistical analyses were done using the SPSS, version 15, statistical software package. BMI and LDL-C were significantly higher in the high-TSH group than in the low-TSH group after adjustment for age, sex, calorie intake, total fat and carbohydrate intakes, and physical activity. No significant differences were found between the groups in TG, cholesterol, and HDL-C. The association between TSH levels andT4 was significant. Individuals with TSH levels at the upper limit of normality might be at risk of hypercholesterolemia and obesity

Hyperthermia and smart drug delivery systems for solid tumor therapy

Chemotherapy is a cornerstone of cancer therapy. Irrespective of the administered drug, it is crucial that adequate drug amounts reach all cancer cells. To achieve this, drugs first need to be absorbed, then enter the blood circulation, diffuse into the tumor interstitial space and finally reach the tumor cells. Next to chemoresistance, one of the most important factors for effective chemotherapy is adequate tumor drug uptake and penetration. Unfortunately, most chemotherapeutic agents do not have favorable properties. These compounds are cleared rapidly, distribute throughout all tissues in the body, with only low tumor drug uptake that is heterogeneously distributed within the tumor. Moreover, the typical microenvironment of solid cancers provides additional hurdles for drug delivery, such as heterogeneous vascular density and perfusion, high interstitial fluid pressure, and abundant stroma. The hope was that nanotechnology will solve most, if not all, of these drug delivery barriers. However, in spite of advances and decades of nanoparticle development, results are unsatisfactory. One promising recent development are nanoparticles which can be steered, and release content triggered by internal or external signals. Here we discuss these so-called smart drug delivery systems in cancer therapy with emphasis on mild hyperthermia as a trigger signal for drug delivery

Applications of biomimetic nanoparticles in breast cancer as a blueprint for improved next-generation cervical cancer therapy

Nanomedicines are innovative and promising, but lack a convincing clinical presence. Thus, biomimetic nanoparticles (BMNPs) have been designed with functionalizations which structurally and/or functionally mimic the biological setting, endowing thereupon biological structure and functionality. These may be coated with biologically derived materials, but may also include artificial antigen-presenting cells and synthetic architectures. When applied in cancer theranostics, BMNPs show significant improvements over traditional drugs and similar non-biomimetic NPs, especially in terms of circulation time, tissue penetration, delivery, and lowered toxicity. These particles have achieved unprecedented outcomes through top-down synthesis methods (cell material to NP), which bypass complex bottom-up synthetic techniques attempting to mimic such complex and diverse biological components. Breast cancer has received much attention in this area, and as such, is studied in this paper as a template for how BMNPs could be applied in cervical cancer – an area with few BMNP applications and a dire need for efficacious and fertility-preserving therapies. This cancer remains an enormous burden globally, especially in developing countries. Being a virus-induced disease, biomimetic applications may be particularly promising, aligning with the emergence of biomimetic nanovaccines in recent years. Feasibility challenges remain within BMNPs: Extracting biological material for re-administration to patients could cause ethical debate, and the costs involved in preparing scaled up quantities of biomimetic NPs would be large. However, with a clearer understanding and tighter characterization of preparation methods and biological responses, BMNPs may add great value to the nanomedicine community.</p

Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells

Introduction: PEGylated liposomes are widely used and studied as carriers for chemotherapeutics. While pharmacokinetics of the encapsulated drug is drastically altered resulting in favorable circulation time, improved tumor accumulation, and better manageable or reduced side effects, therapeutic efficacy has been disappointing. Major drawbacks are a failure to reach the tumor cell, limited penetration depth, and impaired uptake by tumor cells. Materials and methods: Here, we study the implication of HIV-1 transactivator of transcription (TAT)-derived peptides inserted on PEGylated liposomal doxorubicin (PLD) and followed in vitro and in vivo fate. PLDs were installed with 25-400 TAT peptides per liposome without an effect on PLD stability. Results: While TAT peptides facilitate active endocytosis of the carriers, we observed that these peptides did not promote endosomal escape or enhanced intracellular availability of doxorubicin. Interestingly, incorporation of TAT peptides did not change pharmacokinetics or biodistribution, which we found to result from a dysopsonization of the TAT-modified liposomes by serum proteins. A protein corona (PC) on TAT peptide-modified PLDs shields the active moieties and effectively reduces clearance of the TAT peptide containing nanoparticles. However, intratumoral activity was influenced by the number of TAT peptides present. The best antitumor efficacy was observed with a TAT peptide density of 100, while lower amounts showed results comparable to unmodified PLDs. At 200 TAT peptides, the preparation appeared to be least effective, which likely results from augmented interaction with tumor cells directly upon extravasation. Conclusion: We conclude that by optimizing TAT-modified PLDs, the occurring PC balances pharmacokinetics and tumor penetration through interference with avidity

Enhanced Specificity and Drug Delivery in Tumors by cRGD - Anchoring Thermosensitive Liposomes

Purpose: To develop RGD-targeted thermosensitive liposomes with increased tumor retention, improving drug release efficiency upon mild hyperthermia (HT) in both tumor and angiogenic endothelial cells. Methods: Standard termosensitive liposomes (TSL) and TSL containing a cyclic Arg-Gly-Asp (cRGD) pentapeptide with the sequence Arg-Cys-D-Phe-Asp-Gly (RGDf[N-Met]C) were synthetized, loaded with Dox and characterized. Temperature- and time-dependent drug release profiles were assessed by fluorometry. Intracellular Dox delivery was studied by flow cytometry and confocal microscopy. Cytotoxic effect of TSL and RGD-TSL was studied on B16Bl6 melanoma, B16F10 melanoma and HUVEC. Intravital microscopy was performed on B16Bl6 tumors implanted in dorsal-skin fold window-bearing mice. Pharmacokinetic and biodistribution of Dox-TSL and Dox-RGD-TSL were followed in B16Bl6 tumor bearing mice upon normothermia or initial hyperthermia conditions. Results: DLS and cryo-TEM revealed particle homogeneity and size of around 85 nm. Doxorubicin loading efficiency was >95%as assessed by spectrofluorometry. Flow cytometry and confocal microscopy showed a specific uptake of RGD-TSL by melanoma and endothelial cells when compared to TSL and an increased doxorubicin delivery. High resolution intravital microscopy demonstrated specific accumulation of RGD-TSL to the tumor vasculature. Moreover, application of hyperthermia resulted in massive drug release from RGD-TSL. Biodistribution studies showed that initial hyperthermia increases Dox uptake in tumors from TSL and RGD-TSL. Conclusion: RGD-TSL have potency to increase drug efficacy due to higher uptake by tumor and angiogenic endothelial cells in combination with heat-triggered drug release

Modeling the static response and pull-in instability of CNT nanotweezers under the Coulomb and van der Waals attractions

In this paper, the static response and pull-in instability of nanotweezers fabricated from carbon nanotubes (CNT) are theoretically investigated considering the effects of the Coulomb electrostatic and van der Waals molecular attractions. For this purpose, a nanoscale continuum model is employed to obtain the nonlinear constitutive equation of this nano-device. The van der Waals attraction is computed from the simplified Lennard-Jones potential. In order to solve the nonlinear constitutive equation of the nanotweezers, three different approaches, e.g. developing a lumped parameter model, applying the analytical modified Adomian decomposition (MAD) and using a commercial numerical integration routine, are employed. The obtained results are in good agreement with experimental measurements as reported in the literature. As a case study, we have investigated a freestanding nanotweezer and have determined the detachment length and minimum initial gap. Furthermore, range of dominancy of the molecular attraction has been discussed. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved

A Systematic Research and Meta-Synthesis of Studies on the Why of Islamic Psychology School

Muslims with cultural-belief backgrounds demand special psychological services; moreover, the different between Islamic fundamentals and psychology fundamentals needs to establish a school called "Islamic psychology". Studying the why of a school helps facilitate the criticism with the integration of the essentials, determine the direction of movement, and withdraw or make sure of continuing the path. In addition, a systematic research and meta-synthesis of studies is necessary because of the large amount of information in this field. "Systematic research" is a logical method to find all information in a specific field. "Meta-synthesis" is a method by which the differences and similarities of qualitative researches can be compared with combining their findings. In the stage of the systematic research, 37 journals and 33 masters were identified that after reviewing their works, 60 books, 700 papers, and 18 meetings were extracted. In the stage of meta-synthesis, after deleting unrelated documents, 3 books, 14 papers, 7 interviews, and 14 meetings were summarized, coded, categorized, integrated, and rewritten. According to the results, there are two answers for the why of Islamic psychology school: "the shortages of psychology" and "the contents of Islamic psychology school". The shortages of psychology are placed in six headings: bias, error of foundations, cultural-belief incompatibility, methodology limitation, inefficiency, and value-centeredness. The contents are also placed in five headings: available psychological opportunities, religious psychological knowledge, the need to realize a comprehensive and unique approach, Islamic socialization, and benefits of localization