Biosensors for Cancer Biomarkers Based on Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) exhibit highly beneficial characteristics for devising efficient biosensors for different analytes. Their unique properties, such as capabilities for stable covalent binding to recognition groups (e.g., antibodies or aptamers) and sensing surfaces, open a plethora of opportunities for biosensor construction. In addition, their structured porosity offers capabilities for entrapping signaling molecules (dyes or electroactive species), which could be released efficiently in response to a desired analyte for effective optical or electrochemical detection. This work offers an overview of recent research studies (in the last five years) that contain MSNs in their optical and electrochemical sensing platforms for the detection of cancer biomarkers, classified by cancer type. In addition, this study provides an overview of cancer biomarkers, as well as electrochemical and optical detection methods in general.

Direct electrochemical reduction of graphene oxide thin film for aptamer-based selective and highly sensitive detection of matrix metalloproteinase 2.

Simple and low-cost biosensing solutions are suitable for point-of-care applications aiming to overcome the gap between scientific concepts and technological production. To compete with sensitivity and selectivity of golden standards, such as liquid chromatography, the functionalization of biosensors is continuously optimized to enhance the signal and improve their performance, often leading to complex chemical assay development. In this research, the efforts are made on optimizing the methodology for electrochemical reduction of graphene oxide to produce thin film-modified gold electrodes. Under the employed specific conditions, 20 cycles of cyclic voltammetry (CV) are shown to be optimal for superior electrical activation of graphene oxide into electrochemically reduced graphene oxide (ERGO). This platform is further used to develop a matrix metalloproteinase 2 (MMP-2) biosensor, where specific anti-MMP2 aptamers are utilized as a biorecognition element. MMP-2 is a protein which is typically overexpressed in tumor tissues, with important roles in tumor invasion, metastasis as well as in tumor angiogenesis. Based on impedimetric measurements, we were able to detect as low as 3.32 pg mL-1 of MMP-2 in PBS with a dynamic range of 10 pg mL-1 - 10 ng mL-1. Further experiments with real blood samples revealed a promising potential of the developed sensor for direct measurement of MMP-2 in complex media. High specificity of detection is demonstrated - even to the closely related enzyme MMP-9. Finally, the potential of reuse was demonstrated by signal restoration after experimental detection of MMP-2.

Advanced mesoporous silica nanocarriers in cancer theranostics and gene editing applications.

Targeted nanomaterials for cancer theranostics have been the subject of an expanding volume of research studies in recent years. Mesoporous silica nanoparticles (MSNs) are particularly attractive for such applications due to possibilities to synthesize nanoparticles (NPs) of different morphologies, pore diameters and pore arrangements, large surface areas and various options for surface functionalization. Functionalization of MSNs with different organic and inorganic molecules, polymers, surface-attachment of other NPs, loading and entrapping cargo molecules with on-desire release capabilities, lead to seemingly endless prospects for designing advanced nanoconstructs exerting multiple functions, such as simultaneous cancer-targeting, imaging and therapy. Describing composition and multifunctional capabilities of these advanced nanoassemblies for targeted therapy (passive, ligand-functionalized MSNs, stimuli-responsive therapy), including one or more modalities for imaging of tumors, is the subject of this review article, along with an overview of developments within a novel and attractive research trend, comprising the use of MSNs for CRISPR/Cas9 systems delivery and gene editing in cancer. Such advanced nanconstructs exhibit high potential for applications in image-guided therapies and the development of personalized cancer treatment.

pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers.

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.

Magnetic nanoarchitectures for cancer sensing, imaging and therapy.

The use of magnetic nanoparticles for sensing and theranostics of cancer has grown substantially in the last decade. Since the pioneering studies, which reported magnetic nanoparticles for bio-applications more than fifteen years ago, nanomaterials have increased in complexity with different shapes (nanoflowers, nanospheres, nanocubes, nanostars etc.) and compositions (e.g. core-shell) of nanoparticles for an increase in the sensitivity (imaging or sensing) and efficiency through synergistic treatments such as hyperthermia and drug delivery. In this review, we describe recent examples concerning the use of magnetic nanoparticles for bio-applications, from the surface functionalization methods to the development of cancer sensors and nanosystems for magnetic resonance and other imaging methodologies. Multifunctional nanosystems (nanocomposites, core shell nanomaterials) for theranostic applications involving treatments such as hyperthermia, photodynamic therapy, targeted drug delivery, and gene silencing are also described. These nanomaterials could be the future of medicine, although their complexity raises concerns about their safety.

Silicon-based nanotheranostics.

With the rapid expansion of nanoscience and nanotechnology in interdisciplinary fields, multifunctional nanomaterials have attracted particular attention. Recent advances in nanotherapeutics for cancer applications provided diverse groups of synthetic particles with defined cellular and biological functions. The advance of nanotechnology significantly increased the number of possibilities for the construction of diverse biological tools. Such materials are destined to be of great importance because of the opportunity to combine the biotechnological potential of nanoparticles together with the recognition, sensitivity and modulation of cellular pathways or genes when applied to living organisms. In this mini review three main types of Si-based nanomaterials are highlighted in the area of their application for therapy and imaging: porous silicon nanoparticles (pSiNPs), mesoporous silica nanoparticles (MSNs), focusing on their nanoconstructs containing coordination compounds, and periodic mesoporous silica nanoparticles (PMONPs). Moreover, a critical discussion on the research efforts in the construction of nanotheranostics is presented.

Magnetic Field-Induced Accentuation of Drug Release from Core/Shell Magnetic Mesoporous Silica Nanoparticles for Anticancer Treatment.

Drug (9-aminoacridine) loaded core/shell magnetic iron oxide-containing mesoporous silica nanoparticles (MMSN) were treated with HeLa cells and the drug carriers were agitated by expo- sure to magnetic field. Viability studies show the applicability of drug loaded magnetic material for anticancer treatment, which is enhanced upon stimulation with magnetic field. Confocal micrographs of fluorescein grafted MMSN-treated HeLa cells confirmed the ability of magnetic field to concentrate the synthesized material in the exposed area of the cells. The synthesized material and the applied drug delivery method may find application in magnetic field-responsive targeted treatment of cancer.

Ruthenium(ii) complex-photosensitized multifunctionalized porous silicon nanoparticles for two-photon near-infrared light responsive imaging and photodynamic cancer therapy.

Multifunctionalized porous silicon nanoparticles (pSiNPs), containing the novel Ru(ii) complex-photosensitizer, the polyethylene glycol moiety, and mannose molecules as cancer targeting ligands, are constructed and showcased for application in near infrared (NIR) light-responsive photodynamic therapy (PDT) and imaging of cancer. Exposure to NIR light leads to two-photon excitation of the Ru(ii)-complex which allows efficient simultaneous cancer-imaging and targeted PDT therapy with the functionalized biodegradable pSiNP nanocarriers.

Nanodiamond-PMO for two-photon PDT and drug delivery.

In this article, we highlight the properties of nanodiamonds (ND), which were encapsulated in periodic mesoporous organosilica nanoparticles (PMO) and were able to generate reactive oxygen species for photodynamic applications upon two-photon excitation (TPE). The ND@PMO nanoparticles were characterized by various techniques and were then loaded with the anti-cancer drug doxorubicin. The release of the drug was pH sensitive and a synergistic cancer cell killing effect was observed when cancer cells were incubated with doxorubicin-loaded ND@PMO and irradiated with two-photon excitation at 800 nm.

Monomolecular sheets of propeller-shaped triethyl 4,4',4''-[benzene-1,3,5-triyltris(ethyne-2,1-diyl)]tribenzoate deuterochloroform monosolvate.

The title compound, C39H30O6·CDCl3, has a chemical threefold axis and an approximately planar structure, with an ethoxycarbonyl substituent on each of the terminal benzenes oriented in the same direction, thus forming a propeller-shaped molecule. This molecule is of particular interest in the field of metal-organic frameworks (MOFs), where its hydrolyzed analogue forms MOF structures with high surface areas. The benzene ring which occupies the centre of the molecule forms π-π interactions to the equivalent benzene ring at a perpendicular distance of 3.32 (1) Å. Centrosymmetric dimers formed in this way are interconnected by intermolecular C-H···π interactions with a rather short H···CgA distance of 2.51 Š(CgA is the centroid of the central benzene ring). The molecules are arranged in regular parallel sheets. Within a sheet, molecules are interconnected via C-H···O interactions where all carbonyl O atoms participate in weak hydrogen bonds as hydrogen-bond acceptors. Neighbouring sheets are connected through the above-mentioned π-π and C-H···π interactions.

A magnetic mesoporous silica nanoparticle-based drug delivery system for photosensitive cooperative treatment of cancer with a mesopore-capping agent and mesopore-loaded drug.

Lately, there has been a growing interest in anticancer therapy with a combination of different drugs that work by different mechanisms of action, which decreases the possibility that resistant cancer cells will develop. Herein we report on the development of a drug delivery system for photosensitive delivery of a known anticancer drug camptothecin along with cytotoxic cadmium sulfide nanoparticles from a magnetic drug nanocarrier. Core-shell nanoparticles consisting of magnetic iron-oxide-cores and mesoporous silica shells are synthesized with a high surface area (859 m(2) g(-1)) and hexagonal packing of mesopores, which are 2.6 nm in diameter. The mesopores are loaded with anticancer drug camptothecin while entrances of the mesopores are blocked with 2-nitro-5-mercaptobenzyl alcohol functionalized CdS nanoparticles through a photocleavable carbamate linkage. Camptothecin release from this magnetic drug delivery system is successfully triggered upon irradiation with UV light, as measured by fluorescence spectroscopy. Photosensitive anticancer activity of the drug delivery system is monitored by viability studies on Chinese hamster ovarian cells. The treatment of cancer cells with drug loaded magnetic material leads to a decrease in viability of the cells due to the activity of capping CdS nanoparticles. Upon exposure to low power UV light (365 nm) the loaded camptothecin is released which induces additional decrease in viability of CHO cells. Hence, the capping CdS nanoparticles and loaded camptothecin exert a cooperative anticancer activity. Responsiveness to light irradiation and magnetic activity of the nanocarrier enable its potential application for selective targeted treatment of cancer.