Investigating the performance of a novel pH and cathepsin B sensitive, stimulus-responsive nanoparticle for optimised sonodynamic therapy in prostate cancer.

Nano-formulations that are responsive to tumour-related and externally-applied stimuli can offer improved, site-specific antitumor effects, and can improve the efficacy of conventional therapeutic agents. Here, we describe the performance of a novel stimulus-responsive nanoparticulate platform for the targeted treatment of prostate cancer using sonodynamic therapy (SDT). The nanoparticles were prepared by self-assembly of poly(L-glutamic acid-L-tyrosine) co-polymer with hematoporphyrin.

Increased expression of IGF-1Ec with increasing colonic polyp dysplasia and colorectal cancer.

Purpose: IGF-1Ec is an isoform of Insulin-like growth factor 1 (IGF-1) and has recently been identified to be overexpressed in cancers including prostate and neuroendocrine tumours. The aim of this paper is to investigate the expression of IGF-1Ec in colorectal cancer and polyps compared to normal colon tissues and its association with recurrent disease using semi-quantitative immunohistochemistry.

Methods: Immunohistochemistry for IGF-1Ec expression was performed for colorectal cancer, colorectal polyps and normal colonic tissues.

Mechano-growth Factor Expression in Colorectal Cancer Investigated With Fluorescent Gold Nanoparticles.

Background/aim: Fluorescent gold nanoparticles demonstrate strong photoluminescence, photostability, and low cellular toxicity, making them attractive agents for biomedical applications. Mechano-growth factor (MGF) is an isoform of IGF1 and its expression has been demonstrated in malignancies including prostate cancer.

Materials And Methods: Near-infrared-emitting gold nanoparticles (AuNPs) were synthesized and conjugated to MGF.

Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors.

Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells B: 6.

Detection of cell surface calreticulin as a potential cancer biomarker using near-infrared emitting gold nanoclusters.

Calreticulin (CRT) is a cytoplasmic calcium-binding protein. The aim of this study was to investigate CRT presence in cancer with the use of fluorescent gold nanoclusters (AuNCs) and to explore AuNC synthesis using mercaptosuccinic acid (MSA) as a coating agent. MSA-coated AuNCs conferred well-dispersed, bio-stable, water-soluble nanoparticles with bioconjugation capacity and 800-850 nm fluorescence after broad-band excitation.

Demonstration of Calreticulin Expression in Hamster Pancreatic Adenocarcinoma with the Use of Fluorescent Gold Quantum Dots.

Background: There is dire need for discovery of novel pancreatic cancer biomarkers and of agents with the potential for simultaneous diagnostic and therapeutic capacity. This study demonstrates calreticulin expression on hamster pancreatic adenocarcinoma via bio-conjugated gold quantum dots (AuQDs).

Materials And Methods: Hamster pancreatic adenocarcinoma cells were cultured, fixed and incubated with fluorescent AuQDs, bio-conjugated to anti-calreticulin antibodies.

Fumed silica nanoparticle mediated biomimicry for optimal cell-material interactions for artificial organ development.

Replacement of irreversibly damaged organs due to chronic disease, with suitable tissue engineered implants is now a familiar area of interest to clinicians and multidisciplinary scientists. Ideal tissue engineering approaches require scaffolds to be tailor made to mimic physiological environments of interest with specific surface topographical and biological properties for optimal cell-material interactions. This study demonstrates a single-step procedure for inducing biomimicry in a novel nanocomposite base material scaffold, to re-create the extracellular matrix, which is required for stem cell integration and differentiation to mature cells.

Efficacy of the specific endothelin a receptor antagonist zibotentan (ZD4054) in colorectal cancer: a preclinical study.

Endothelin 1 (ET-1) is overexpressed in cancer, contributing to disease progression. We previously showed that ET-1 stimulated proliferative, migratory, and contractile tumorigenic effects via the ET(A) receptor. Here, for the first time, we evaluate zibotentan, a specific ET(A) receptor antagonist, in the setting of colorectal cancer, in cellular models.

Interaction between soluble and membrane-embedded potassium channel peptides monitored by Fourier transform infrared spectroscopy.

Recent studies have explored the utility of Fourier transform infrared spectroscopy (FTIR) in dynamic monitoring of soluble protein-protein interactions. Here, we investigated the applicability of FTIR to detect interaction between synthetic soluble and phospholipid-embedded peptides corresponding to, respectively, a voltage-gated potassium (Kv) channel inactivation domain (ID) and S4-S6 of the Shaker Kv channel (KV1; including the S4-S5 linker "pre-inactivation" ID binding site). KV1 was predominantly α-helical at 30°C when incorporated into dimyristoyl-l-α-phosphatidylcholine (DMPC) bilayers.

A novel POSS-coated quantum dot for biological application.

Quantum dots (QDs) are fluorescent semiconductor nanocrystals that have the potential for major advancements in the field of nanomedicine through their unique photophysical properties. They can potentially be used as fluorescent probes for various biomedical imaging applications, including cancer localization, detection of micrometastasis, image guided surgery, and targeted drug delivery. Their main limitation is toxicity, which requires a biologically compatible surface coating to shield the toxic core from the surrounding environment.

Synthesis of mercaptosuccinic acid/MercaptoPolyhedral oligomeric silsesquioxane coated cadmium telluride quantum dots in cell labeling applications.

An aqueous synthesis method to obtain highly luminescent cadmium telluride nanocrystals is described. We have shown water-soluble semi-conductor quantum dots with high photoluminescence quantum yield have great potential for biological applications. The spectral properties of these nanocrystals can be easily tuned according to their particle size to yield multicolours simultaneously by a single excitation light source.

Biofunctionalized quantum dots for live monitoring of stem cells: applications in regenerative medicine.

Aim: This study aimed to live monitor the degree of endothelial progenitor cell (EPC) integration onto tissue-engineering scaffolds by conjugating relevant antibodies to quantum dots (QDs).

Materials & Methods: Biocompatible mercaptosuccinic acid-coated QDs were functionalized with two different antibodies to EPC (CD133 with QDs of 640 nm wavelength [λ] and later-stage mature EPCs; and von Willebrand factor with QDs of λ595 and λ555 nm) using conventional carbomide and N-hydroxysuccinimide chemistry. Biofunctionalization was characterized with Fourier-transform infrared spectroscopy.

Fluorescence nanoparticles "quantum dots" as drug delivery system and their toxicity: a review.

Fluorescence nanocrystals or quantum dots (QDs) are engineered nanoparticles (NP) that have shown great promise with potential for many biological and biomedical applications, especially in drug delivery/activation and cellular imaging. The use of nanotechnology in medicine directed to drug delivery is set to expand in the coming years. However, it is unclear whether QDs, which are defined as NPs rather than small molecules, can specifically and effectively deliver drugs to molecular targets at subcellular levels.

The anti-calcification potential of a silsesquioxane nanocomposite polymer under in vitro conditions: potential material for synthetic leaflet heart valve.

Calcification currently represents a major cause of failure of biological tissue heart valves. It is a complex phenomenon influenced by a number of biochemical and mechanical factors. Recent advances in material science offer new polymers with improved properties, potentially suitable for synthetic leaflets heart valves manufacturing.

In situ endothelialization potential of a biofunctionalised nanocomposite biomaterial-based small diameter bypass graft.

Endothelial dysfunction or the lack of an endothelium associated with cardiovascular grafts is a major cause of graft failure which is linked to thrombosis and related complications. This study was aimed to (1) biofunctionalise a nanocomposite biomaterial, Polyhedral Oligomeric silsesquioxane modified polycarbonate urea-urethane (POSS-PCU), based small diameter vascular graft and to (2) induce endothelialization with EPC containing monocytes, which were extracted from peripheral blood. (1) Biofunctionalisation of the nanocomposite polymer: bioactive RGD peptide, which is a functional domain of an extracellular matrix component, fibronectin, was synthesised using fmoc chemistry.

Divalent metal-dependent regulation of hepcidin expression by MTF-1.

Hepcidin is a small acute phase peptide that regulates iron absorption. It is induced by inflammation and infection, but is repressed by anaemia and hypoxia. Here we further reveal that hepcidin transcription also involves interactions between functional metal response elements (MREs) in its promoter, and the MRE-binding transcription factor-1.

Engineering a single-chain Fv antibody to alpha v beta 6 integrin using the specificity-determining loop of a foot-and-mouth disease virus.

The alpha v beta 6 integrin is a promising target for cancer therapy. Its expression is up-regulated de novo on many types of carcinoma where it may activate transforming growth factor-beta1 and transforming growth factor-beta 3, interact with the specific extracellular matrix proteins and promote migration and invasion of tumor cells. The viral protein 1 (VP1) coat protein of the O(1) British field strain serotype of foot-and-mouth disease virus is a high-affinity ligand for alpha v beta 6, and we recently reported that a peptide derived from VP1 exhibited alpha v beta 6-specific binding in vitro and in vivo.

Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH.

Backgrounds & Aims: Hepcidin is an acute-phase response peptide. We have investigated the possible involvement of hepcidin in massive obesity, a state of chronic low-grade inflammation. Three groups of severely obese patients with or without diabetes or nonalcoholic steatohepatitis were investigated.

Incorporation of a lauric acid-conjugated GRGDS peptide directly into the matrix of a poly(carbonate-urea)urethane polymer for use in cardiovascular bypass graft applications.

Gly-Arg-Gly-Asp-Ser (GRGDS) was modified by conjugation to lauric acid (LA) to facilitate incorporation into the matrix of a poly(carbonate-urea)urethane (PCU) used in vascular bypass grafts. GRGDS and LA-GRGDS were synthesized using solid phase Fmoc chemistry and characterized by high performance liquid chromatography and Fourier transform infrared spectroscopy. LA-GRGDS was passively coated and incorporated as nanoparticle dispersion on the PCU films.

A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia.

The ischemic stroke is the third leading cause of death in developed countries. The C-terminal peptide of mechano-growth factor (MGF), an alternatively spliced variant of insulin-like growth factor 1 (IGF-1), was found to function independently from the rest of the molecule and showed a neuroprotective effect in vivo and in vitro. In vivo, in a gerbil model of transient brain ischemia, treatment with the synthetic MGF C-terminal peptide provided very significant protection to the vulnerable neurons.

Inhibition of iron transport across human intestinal epithelial cells by hepcidin.

We investigated the effects of the iron regulatory peptide hepcidin on iron transport by the human intestinal epithelial Caco-2 cell line. Caco-2 cells were exposed to hepcidin for 24 hours prior to the measurement of both iron transport and transporter protein and mRNA expression. Incubation with hepcidin significantly decreased apical iron uptake by Caco-2 cells.

Structural stability and heat-induced conformational change of two complement inhibitors: C4b-binding protein and factor H.

The complement inhibitors C4b-binding protein (C4BP) and factor H (FH) both consist of complement control protein (CCP) domains. Here we examined the secondary structure of both proteins by circular dichroism and Fourier-transform infrared technique at temperatures ranging from 30 degrees C-90 degrees C. We found that predominantly beta-sheet structure of both proteins was stable up to 70 degrees C, and that a reversible conformational change toward alpha-helix was apparent at temperatures ranging from 70 degrees C to 90 degrees C.