Porous Inorganic Carriers Based on Silica, Calcium Carbonate and Calcium Phosphate for Controlled/Modulated Drug Delivery: Fresh Outlook and Future Perspectives

Porous inorganic nanostructured materials are widely used nowadays as drug delivery carriers due to their adventurous features: suitable architecture, large surface area and stability in the biological fluids. Among the different types of inorganic porous materials, silica, calcium carbonate, and calcium phosphate have received significant attention in the last decade. The use of porous inorganic materials as drug carriers for cancer therapy, gene delivery etc. has the potential to improve the life expectancy of the patients affected by the disease. The main goal of this review is to provide general information on the current state of the art of synthesis of the inorganic porous particles based on silica, calcium carbonate and calcium phosphate. Special focus is dedicated to the loading capacity, controllable release of drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic field, and ultrasound). Moreover, the diverse compounds to deliver with silica, calcium carbonate and calcium phosphate particles, ranging from the commercial drugs to genetic materials are also discussed

Synthesis and Functionalization of Monodisperse Near-ultraviolet and Visible Excitable Multifunctional Eu3+, Bi3+:REVO4 Nanophosphors for Bioimaging and Biosensing Applications

Near-ultraviolet and visible excitable Eu- and Bi-doped NPs based on rare earth vanadates (REVO4, RE = Y, Gd) have been synthesized by a facile route from appropriate RE precursors, europium and bismuth nitrate, and sodium orthovanadate, by homogeneous precipitation in an ethylene glycol/water mixture at 120 °C. The NPs can be functionalized either by a one-pot synthesis with polyacrylic acid (PAA) or by a Layer-by-Layer approach with poly(allylamine hydrochloride) (PAH) and PAA. In the first case, the particle size can also be tuned by adjusting the amount of PAA. The Eu- Bi-doped REVO4 based nanophosphors show the typical red luminescence of Eu(III), which can be excited through an energy transfer process from the vanadate anions, resulting in a much higher luminescence intensity in comparison to the direct excitation of the europium cations. The incorporation of Bi into the REVO4 structure shifts the original absorption band of the vanadate anions towards longer wavelengths, giving rise to nanophosphors with an excitation maximum at 342 nm, which can also be excited in the visible range. The suitability of such nanophosphors for bioimaging and biosensing applications, as well as their colloidal stability in different buffer media of biological interest, their cytotoxicity, their degradability at low pH, and their uptake by HeLa cells have been evaluated. Their suitability for bioimaging and biosensing applications is also demonstrated.European Union 267226Ministerio de Economía y Competitividad MAT2014-54852-

Rare earth based nanostructured materials: Synthesis, functionalization, properties and bioimaging and biosensing applications

Rare earth based nanostructures constitute a type of functional materials widely used and studied in the recent literature. The purpose of this review is to provide a general and comprehensive overview of the current state of the art, with special focus on the commonly employed synthesis methods and functionalization strategies of rare earth based nanoparticles and on their different bioimaging and biosensing applications. The luminescent (including downconversion, upconversion and permanent luminescence) and magnetic properties of rare earth based nanoparticles, as well as their ability to absorb X-rays, will also be explained and connected with their luminescent, magnetic resonance and X-ray computed tomography bioimaging applications, respectively. This review is not only restricted to nanoparticles, and recent advances reported for in other nanostructures containing rare earths, such as metal organic frameworks and lanthanide complexes conjugated with biological structures, will also be commented on.European Union 267226Ministerio de Economía y Competitividad MAT2014-54852-

Current outlook on radionuclide delivery systems: from design consideration to translation into clinics

Radiopharmaceuticals have proven to be effective agents, since they can be successfully applied for both diagnostics and therapy. Effective application of relevant radionuclides in pre-clinical and clinical studies depends on the choice of a sufficient delivery platform. Herein, we provide a comprehensive review on the most relevant aspects in radionuclide delivery using the most employed carrier systems, including, (i) monoclonal antibodies and their fragments, (ii) organic and (iii) inorganic nanoparticles, and (iv) microspheres. This review offers an extensive analysis of radionuclide delivery systems, the approaches of their modification and radiolabeling strategies with the further prospects of their implementation in multimodal imaging and disease curing. Finally, the comparative outlook on the carriers and radionuclide choice, as well as on the targeting efficiency of the developed systems is discussed

Optically responsive delivery platforms: from the design considerations to biomedical applications

Drug carriers with intelligent functions are powerful therapeutic and diagnostic platforms in curing various diseases such as malignant neoplasms. These functions include the remote noninvasive activation of drug using physical impacts, e.g. light exposure. Combination of different therapeutic modalities (chemotherapy, photodynamic therapy, and so forth) with light-responsive carriers enables promising synergetic effect in tumour treatment. The main goal of this review article is to provide the state of the art on light-sensitive delivery systems with the identification of future directions and their implementation in tumour treatment. In particular, this article reviews the general information on the physical and chemical fundamental mechanisms of interaction between light and carrier systems (e.g. plasmonic and dielectric nanoparticles), the design of optically responsive drug carriers (plain and composite), and the mechanisms of light-driven controlled release of bioactive compounds in biological environment. The special focus is dedicated to the most recent advances in optically responsive bioinspired drug vehicles

Modelling Human-like Behavior through Reward-based Approach in a First-Person Shooter Game

We present two examples of how human-like behavior can be implemented in a model of computer player to improve its characteristics and decision-making patterns in video game. At first, we describe a reinforcement learning model, which helps to choose the best weapon depending on reward values obtained from shooting combat situations.Secondly, we consider an obstacle avoiding path planning adapted to the tactical visibility measure. We describe an implementation of a smoothing path model, which allows the use of penalties (negative rewards) for walking through \bad" tactical positions. We also study algorithms of path nding such as improved I-ARA* search algorithm for dynamic graph by copying human discrete decision-making model of reconsidering goals similar to Page-Rank algorithm. All the approaches demonstrate how human behavior can be modeled in applications with significant perception of intellectual agent actions

Modelling Human-like Behavior through Reward-based Approach in a First-Person Shooter Game

We present two examples of how human-like behavior can be implemented in a model of computer player to improve its characteristics and decision-making patterns in video game. At first, we describe a reinforcement learning model, which helps to choose the best weapon depending on reward values obtained from shooting combat situations.Secondly, we consider an obstacle avoiding path planning adapted to the tactical visibility measure. We describe an implementation of a smoothing path model, which allows the use of penalties (negative rewards) for walking through \bad" tactical positions. We also study algorithms of path nding such as improved I-ARA* search algorithm for dynamic graph by copying human discrete decision-making model of reconsidering goals similar to Page-Rank algorithm. All the approaches demonstrate how human behavior can be modeled in applications with significant perception of intellectual agent actions

Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models

The search for new criteria indicating acute or chronic pathological processes resulting from exposure to toxic agents, testing of drugs for potential hepatotoxicity, and fundamental study of the mechanisms of hepatotoxicity at a molecular level still represents a challenging issue that requires the selection of adequate research models and tools. Microfluidic chips (MFCs) offer a promising in vitro model for express analysis and are easy to implement. However, to obtain comprehensive information, more complex models are needed. A fundamentally new label-free approach for studying liver pathology is fluorescence-lifetime imaging microscopy (FLIM). We obtained FLIM data on both the free and bound forms of NAD(P)H, which is associated with different metabolic pathways. In clinical cases, liver pathology resulting from overdoses is most often as a result of acetaminophen (APAP) or alcohol (ethanol). Therefore, we have studied and compared the metabolic state of hepatocytes in various experimental models of APAP and ethanol hepatotoxicity. We have determined the potential diagnostic criteria including the pathologically altered metabolism of the hepatocytes in the early stages of toxic damage, including pronounced changes in the contribution from the bound form of NAD(P)H. In contrast to the MFCs, the changes in the metabolic state of hepatocytes in the ex vivo models are, to a greater extent, associated with compensatory processes. Thus, MFCs in combination with FLIM can be applied as an effective tool set for the express modeling and diagnosis of hepatotoxicity in clinics

Photoluminescence quenching of dye molecules near a resonant silicon nanoparticle

Luminescent molecules attached to resonant colloidal particles are an important tool to study light-matter interaction. A traditional approach to enhance the photoluminescence intensity of the luminescent molecules in such conjugates is to incorporate spacer-coated plasmonic nanoantennas, where the spacer prevents intense non-radiative decay of the luminescent molecules. Here, we explore the capabilities of an alternative platform for photoluminescence enhancement, which is based on low-loss Mie-resonant colloidal silicon particles. We demonstrate that resonant silicon particles of spherical shape are more efficient for photoluminescence enhancement than their plasmonic counterparts in spacer-free configuration. Our theoretical calculations show that significant enhancement originates from larger quantum yields supported by silicon particles and their resonant features. Our results prove the potential of high-index dielectric particles for spacer-free enhancement of photoluminescence, which potentially could be a future platform for bioimaging and nanolasers