MicroRNA-30a-5pme: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples

Abstract Background The rising incidence of renal cell carcinomas (RCC) constitutes a significant challenge owing to risk of overtreatment. Because aberrant microRNA (miR) promoter methylation contributes to cancer development, we investigated whether altered miR-30a-5p expression associates with DNA promoter methylation and evaluated the usefulness as clear cell RCC (ccRCC) diagnostic and prognostic markers. Methods Genome-wide methylome and RNA sequencing data from a set of ccRCC and normal tissue samples from The Cancer Genome Atlas (TCGA) database were integrated to identify candidate CpG loci involved in cancer onset. MiR-30a-5p expression and promoter methylation were quantitatively a…

Nanoscopic hybrid systems with a polarity-controlled gate-like scaffolding for the colorimetric signalling of long-chain carboxylates

Hybrid mesoporous systems containing a gate-like ensemble functionalised with imidazolium groups and a dye are used for the selective colorimetric sensing of long-chain carboxylates. Amoros del Toro, Pedro Jose, Pedro.Amoros@uv.es

Controlled release using mesoporous materials containing gate-like scaffoldings.

The use of gated mesoporous silica solids as suitable systems for controlled-release protocols is reviewed. These materials are based on mesoporous silica supports that can be prepared with tailor-made pores of around 2 - 10 nm and that show a very large specific surface area (up to 1200 m(2)/g), thus having a large load capacity. The solids can be additionally functionalised in the external surface with gate-like systems that can be opened on command to allow cargo release. Light, redox reactions, pH, temperature, polarity and enzyme-driven protocols are shown. The possible application in drug delivery protocols is discussed.

Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with "Saccharides"

The synthesis of new capped silica mesoporous nanoparticles for on-command delivery applications is described. The gate-like functional hybrid systems consisted of nanoscopic MCM-41-based materials functionalized on the pore outlets with different “saccharide” derivatives and a dye contained in the mesopores. A series of hydrolyzed starch products as saccharides were selected. The mesoporous silica nanoparticles S1, S2, and S3 containing the grafted starch derivatives Glucidex 47, Gludicex 39, and Glucidex 29 were synthesized. Additionally, for comparative purposes solid S4 containing lactose was prepared. Delivery studies in pure water in the presence of pancreatin or -D-galactosidase were…

Oligonucleotide-capped mesoporous silica nanoparticles as DNA-responsive dye delivery systems for genomic DNA detection

[EN] New hybrid oligonucleotide-capped mesoporous silica nanoparticles able to detect genomic DNA were designed.

Towards chemical communication between gated nanoparticles.

The design of comparatively simple and modularly configurable artificial systems able to communicate through the exchange of chemical messengers is, to the best of our knowledge, an unexplored field. As a proof-of-concept, we present here a family of nanoparticles that have been designed to communicate with one another in a hierarchical manner. The concept involves the use of capped mesoporous silica supports in which the messenger delivered by a first type of gated nanoparticle is used to open a second type of nanoparticle, which delivers another messenger that opens a third group of gated nanoobjects.We believe that the conceptual idea that nanodevices can be designed to communicate with …

Borate-driven gatelike scaffolding using mesoporous materials functionalised with saccharides.

We report the development of an MCM-41 mesoporous support that is functionalised with saccharides at the pore outlets and contains the dye [Ru(bipy)(3)](2+) in the pores (solid S1; bipy = 2,2'-bipyridyl). For this hybrid system, the inhibition of mass transport of the dye from the pore voids to the bulk solution in the presence of borate is demonstrated in water at neutral pH. The formation of the corresponding boroester derivative is related to the selective reaction of borate with the appended saccharides. This control is selective and only anion borate, among several anions and cations, can act as a molecular tap and inhibit the delivery of the entrapped guest. Additionally, the S1-borat…

Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration

This article focuses on the study of the release rate in a family of modified silica mesoporous supports. A collection of solids containing ethyl, butyl, hexyl, octyl, decyl, octadecyl, docosyl, and triacontyl groups anchored on the pore outlets of mesoporous MCM-41 has been prepared and characterized. Controlled release from pore voids has been studied through the delivery of the dye complex tris(2,2¿-bipyridyl)ruthenium(II). Delivery rates were found to be dependent on the alkyl chain length anchored on the pore outlets of the mesoporous scaffolding. Moreover, release rates follow a Higuchi diffusion model, and Higuchi constants for the different hybrid solids have been calculated. A decr…

Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles.

[EN] A new gated nanodevice design able to control cargo delivery using glucose as a trigger and cyclodextrin-modified glucose oxidase as a capping agent is reported.

Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au–Mesoporous Silica Nanoparticles

[EN] This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular b-cyclodextrin: benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeuti…

A new 8-oxo-7,8-2 ' deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine

Many important human diseases, and especially cancer, have been related to the overproduction of 8-oxo-7,8-dihydro-2 '-deoxyguanosine (8-oxo-dG). This molecule is a product of oxidative stress processes over nucleophilic bases in DNA. In this work, an aptasensor for the rapid, selective and accurate detection of this oncomarker is presented. The aptasensor consists of a nanoporous anodic alumina material loaded with a dye and is functionalized with an aptamer-based "molecular gate". In the presence of target 8-oxo-dG, the capping aptamer displaces from the surface due to the high affinity of the analyte with the capping aptamer, thus inducing delivery of the preloaded fluorescent dye. In co…

Dual Enzyme-Triggered Controlled Release on Capped Nanometric Silica Mesoporous Supports

The development of nanoscopic hybrid materials equipped with “molecular gates” showing the ability of releasing target entrapped guests upon the application of an external trigger has attracted great attention and has been extensively explored during recent years.1 These nanodevices are composed of two subunits, namely, a suitable support and certain capping entities grafted on the surface of the scaffolding.2 The support is used as a suitable reservoir in which certain chemicals can be stored whereas the molecules grafted in the outer surface act as a “gate” and can control the release of the entrapped molecules at will. Both components are carefully selected and arranged in order to achie…

Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome

[EN] Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large on…

Poly(N-isopropylacrylamide)-gated Fe3O4/SiO2 core shell nanoparticles with expanded mesoporous structures for the temperature triggered release of lysozyme

Core-shell nanoparticles comprised of Fe3O4 cores and a mesoporous silica shell with an average expanded pore size of 6.07 nm and coated with a poly(N-isopropylacrylamide) (PNIPAM) layer (CS MSNs EP PNIPAM) were prepared and characterized. The nanoparticles was loaded with (Ru(bipy)3 2+) dye or an antibacterial enzyme, lysozyme, to obtain CS MSNs EP PNIPAM Ru(bipy)3 2+ and CS MSNs EP PNIPAM Lys, respectively. The lysozyme loading was determined to be 160 mg/g of nanoparticle. It was seen that Ru(bipy)3 2+ and lysozyme release was minimal at a room temperature of 25 ºC while at physiological temperature (37 º C), abrupt release was observed. The applicability of the CS MSNs EP PNIPAM Lys was…

One-dimensional metal-organic framework with unprecedented heptanuclear copper units.

The reaction of copper(II) sulfate, copper(II) chloride, 3,5-diacetylamino-1,2,4-triazole, and 3-acetylamino-5-amino-1,2,4-triazole in water yields green, plate-shaped crystals of [[{Cu3(mu3-OH(1/2))L(H2O)2Cl}2{mu-Cu(H2O)2Cl2}].12H2O]n (1), where L is a new triazole-derived macrocyclic ligand. The structure of 1 consists of heptanuclear (H)OCuII(3)-CuII-CuII(3)O(H) entities linked in pairs through symmetric mu3-O...H...O-mu3 hydrogen bonds to form a double-stranded one-dimensional network. A significant overall antiferromagnetic behavior has been observed for 1.

Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles

MCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzymes, a zero release system was obtained. S1 was prepared by loading nanoparticles with Safranine O dye and was then capped with a gluconamide derivative. In the absence of enzymes, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase…

New Methods for Anion Recognition and Signaling Using Nanoscopic Gatelike Scaffoldings

Design of enzyme-mediated controlled release systems based on silica mesoporous supports capped with ester-glycol groups

[EN] An ethylene glycol-capped hybrid material for the controlled release of molecules in the presence of esterase enzyme has been prepared. The final organic-inorganic hybrid solid S1 was synthesized by a two-step procedure. In the first step, the pores of an inorganic MCM-41 support (in the form of nanoparticles) were loaded with [Ru(bipy) 3]Cl 2 complex, and then, in the second step, the pore outlets were functionalized with ester glycol moieties that acted as molecular caps. In the absence of an enzyme, release of the complex from aqueous suspensions of S1 at pH 8.0 is inhibited due to the steric hindrance imposed by the bulky ester glycol moieties. Upon addition of esterase enzyme, del…

Über den chemischen Informationsaustausch zwischen gesteuerten Nanopartikeln

Das Design von vergleichsweise einfachen und modular konfigurierbaren k nstlichen Systemen, die ber den Austausch von chemischen Botenstoffen miteinander kommunizieren kçnnen, ist unseres Wissens ein bislang unerforschtes Gebiet. In einer grundlegenden Arbeit pr sentieren wir hier eine Serie von Nanopartikeln, die in hierarchischer Art und Weise miteinander kommunizieren kçnnen. Das Konzept beruht auf gedeckelten mesoporçsen Silikat-Tr gern, bei denen der aus einem ersten Typ von gesteuerten Nanopartikeln freigesetzte chemische Botenstoff einen zweiten Typ von gedeckelten Nanopartikeln çffnet, welche wiederum einen anderen Botenstoff freisetzen, die eine dritte Gruppe von gesteuerten Nanoob…

Selective and Sensitive Chromofluorogenic Detection of the Sulfite Anion in Water Using Hydrophobic Hybrid Organic-Inorganic Silica Nanoparticles

[EN] In water and wine: Chromofluorogenic detection of the sulfite anion in pure water was accomplished by using a new hybrid organic-inorganic material that contained a probe entrapped in hydrophobic biomimetic cavities. This material was used for the detection of sulfite in red wine. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluorogenic Sensing of Carcinogenic Bisphenol A using Aptamer-Capped Mesoporous Silica Nanoparticles

[EN] Mesoporous silica nanoparticles loaded with rhodamine B and capped with a bisphenol A aptamer were used for the selective and sensitive detection of this lethal chemical. The pores of the nanoparticles are selectively opened in the presence of bisphenol A (through its selective coordination with the aptamer) with subsequent rhodamine B delivery. With this capped material a limit of detection as low as 3.5 mu m of bisphenol A was measured.

Fatty Acid Carboxylate- and Anionic Surfactant-Controlled Delivery Systems That Use Mesoporous Silica Supports

We report the preparation of a MCM-41 mesoporous material that contains the dye [Ru(bipy) 3 ]Cl 2 (bipy= bipyridine) inside the mesopores and functionalised with suitable binding groups at the entrance of the pores. Solids S1―S3 were obtained by the reaction of the mesoporous material with N-methyl-N'-propyltrimethoxysilylimidazolium chloride, N-phenyl-N'-[3-(trimethoxysilyl)propyl]thiourea, or N-phenyl-N'-[3-(trimethoxysilyl)propy1]urea, respectively. A study of the dye delivery of these systems in buffered water (pH 7.0, 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES), 10 ―3 mol dm ―3 ) in the presence of a family of carboxylate ions was carried out. In the interaction of …

Additional file 4 of MicroRNA-30a-5pme: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples

Additional file 4 Supplementary Table 1. Univariable and multivariable analysis of clinicopathological and epigenetic variables in TCGA Cohort (OS and RFS). Supplementary Table 2. List of primers’ sequence for qMSP analysis. Supplementary Table 3. qMSP primers’ design within the methylated gene’s sequence. Supplementary Table 4. Cox univariable and multivariable analysis of clinicopathological and epigenetic variables in Cohort #1 (DFS). Supplementary Table 5. Cox univariable analysis of clinicopathological and epigenetic variables in Cohort #1 (DSS). Supplementary Table 6. Cox univariable and multivariable analysis of clinicopathological and epigenetic variables in Cohort #2 (MFS). Supplem…

Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose

Oligonucleotide-capped nanoporous anodic alumina biosensor as diagnostic tool for rapid and accurate detection of Candida auris in clinical samples.

[EN] Candida auris has arisen as an important multidrug-resistant fungus because of several nosocomial outbreaks and elevated rates of mortality. Accurate and rapid diagnosis of C. auris is highly desired; nevertheless, current methods often present severe limitations and produce misidentification. Herein a sensitive, selective, and time-competitive biosensor based on oligonucleotide-gated nanomaterials for effective detection of C. auris is presented. In the proposed design, a nanoporous anodic alumina scaffold is filled with the fluorescent indicator rhodamine B and the pores blocked with different oligonucleotides capable of specifically recognize C. auris genomic DNA. Gate opening modul…

A gated material as immunosensor for in-tissue detection of IDH1-R132H mutation in gliomas

[EN] A nanodevice consisted on nanoporous anodic alumina (NAA) supports functionalized with specific and selective antibody-based gatekeepers for the detection of IDH1-R132H mutant enzyme is here reported. Molecular profile and tissue mutations of the tumours (such as IDH1/IDH2 mutations in gliomas) are a great source of information that already make a difference in terms of prognosis and prediction of response to combined therapy. However, standardized methodologies to determine this mutation are time-consuming and cannot provide information before or during surgical intervention, which significantly limits their utility in terms of intraoperative decisionmaking. To solve this limitation, …

Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells

In recent years, mesoporous silica nanoparticles (MSNs) have been used as effective supports for the development of controlled-release nanodevices that are able to act as multifunctional delivery platforms for the encapsulation of therapeutic agents, enhancing their bioavailability and overcoming common issues such as poor water solubility and poor stability of some drugs. In particular, redox-responsive delivery systems have attracted the attention of scientists because of the intracellular reductive environment related to a high concentration of glutathione (GSH). In this context, we describe herein the development of a GSH-responsive delivery system based on poly(ethylene glycol)- (PEG-)…

Photochemical and Chemical Two-Channel Control of Functional Nanogated Hybrid Architectures

Enhanced Efficacy and Broadening of Antibacterial Action of Drugs via the Use of Capped Mesoporous Nanoparticles

[EN] A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with epsilon-poly-L-lysine (epsilon-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug epsilon-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated.

Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles

[EN] Trapped: Mesoporous silica nanoparticles were loaded with a fluorescent guest and functionalized with octadecyltrimethoxysilane. The alkyl chains interact with paraffins, which build a hydrophobic layer around the particle (see picture). Upon melting of the paraffin, the guest molecule is released, as demonstrated in cells for the guest doxorubicin. The release temperature can be tuned by choosing an appropriate paraffin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Coordinative Versatility of Guanazole [3,5‐Diamino‐1,2,4‐triazole]: Synthesis, Crystal Structure, EPR, and Magnetic Properties of a Dinuclear and a Linear Trinuclear Copper(II) Complex Containing Small Bridges and Triazole Ligands

New complexes with guanazole (3,5-diamino-1,2,4-triazole = Hdatrz), [Cu 2 (Hdatrz) 2 (μ-OH 2 )(H 2 O) 4 (SO 4 )](SO 4 )·3.5H 2 O (1) and [Cu 3 (Hdatrz) 4 (μ-Cl) 2 (H 2 O) 4 (SO 4 ) 2 ]·11.4H 2 O (2), have been prepared and structurally characterized. Complex 1 is a noncentrosymmetric dinuclear compound in which the cop-per(II) ions are bridged by two triazole ligands and one μ-OH 2 molecule, with a Cu(1)···Cu(2) distance of 3.4945(8) A. The chromophores are Cu(1)N 2 O 2 O' (square pyramidal), and Cu(2)N 2 O 2 O'O" (octahedral). Complex 2 has a linear trinuclear copper(II) structure, with two crystallographically independent copper(II) atoms. Neighboring copper(II) ions are linked by two tri…

Additional file 2 of MicroRNA-30a-5pme: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples

Additional file 2 Supplementary Figure S2. Prognostic value of stage and nuclear grade in Cohort #1. (A) Disease-free and (B) disease-specific Kaplan-Meier survival curves based on clinicopathological stage and nuclear grade (Log-rank test).

Additional file 1 of MicroRNA-30a-5pme: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples

Additional file 1 Supplementary Figure S1. Expression of miR-30a-5p according to clinicopathological variables in Cohort #1. Scatter plots of miR-30a-5p expression levels according to metastasis presentation, recurrence and Führman grade (Mann–Whitney U test).

Additional file 3 of MicroRNA-30a-5pme: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples

Additional file 3 Supplementary Figure S3. MiR-30a-5pme levels and prognostic value of stage and nuclear grade in Cohort #2 (A) Scatter plots of miR-30a-5pme levels according to pathological stage (Mann–Whitney U test); (B) Disease-specific and (C) Metastasis-free Kaplan-Meier survival curves based on clinicopathological stage and nuclear grade (Log-rank test).