Alejandro Baeza

Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery

Introduction: Mesoporous silica nanoparticles (MSNPs) are one of the most promising inorganic drug delivery systems (DDSs). The design and development of tumour-targeted MSNPs with stimuli-responsive drug release capability aim at enhancing the efficiency and minimising the side effects of anti-tumour drugs for cancer therapy. Areas covered: This review provides an overview of the scientific advances in MSNPs for tumour-targeted stimuli-responsive drug delivery. The key factors that govern the passive accumulation of MSNPs within solid tumours such as size, shape and surface functionalisation are roughly described. The different active targeting strategies for the specific retention and uptake of MSNPs by tumour cells are also outlined. The approaches developed so far for the synthesis of smart MSNPs capable of releasing the trapped drugs in response to internal or external stimuli and their applications are reviewed. Critical considerations in the use of MSNPs for the treatment of cancer treatment are discussed. The future prospects and key factors concerning the clinical application of MSNPs are considered throughout the manuscript. Expert opinion: MSNPs are promising nanocarriers to efficiently transport and site-specifically deliver highly toxic drugs, such as chemotherapeutic agents for cancer treatment. However, there are certain issues that should be overcome to improve the suitability of MSNPs for clinical applications. Increasing the penetration capability of MSNPs within tumour tissues, providing them of appropriate colloidal stability in physiological fluids and ensuring that their active targeting capability and stimuli-responsive performance are preserved in complex biological media are of foremost significance. Few in vivo evaluation tests of MSNPs have been reported and much research effort into this field is mandatory to be able to move from bench to bedside.

Asymmetric Hybrid Silica Nanomotors for Capture and Cargo Transport: Towards a Novel Motion‐Based DNA Sensor

An innovative self-propelled nanodevice able to perform motion, cargo transport, and target recognition is presented. The system is based on a mesoporous motor particle, which is asymmetrically functionalized by the attachment of single-stranded DNA onto one of its faces, while catalase is immobilized on the other face. This enzyme allows catalytic decomposition of hydrogen peroxide to oxygen and water, giving rise to the driving force for the motion of the whole system. Moreover the motor particles are able to capture and transport cargo particles functionalized with a noncomplementary single-stranded DNA molecule, only if a specific oligonucleotide sequence is present in the media. Functionalization with characteristic oligonucleotide sequences in the system implies a potential for further developments for lab-on-chip devices with applications in biomedical applications.

Magnetic-Responsive Release Controlled by Hot Spot Effect

Magnetically triggered drug delivery nanodevices have attracted great attention in nanomedicine, as they can feature as smart carriers releasing their payload at clinicians will. The key principle of these devices is based on the properties of magnetic cores to generate thermal energy in the presence of an alternating magnetic field. Then, the temperature increase triggers the drug release. Despite this potential, the rapid heat dissipation in living tissues is a serious hindrance for their clinical application. It is hypothesized that magnetic cores could act as hot spots, this is, produce enough heat to trigger the release without the necessity to increase the global temperature. Herein, a nanocarrier has been designed to respond when the temperature reaches 43 °C. This material has been able to release its payload under an alternating magnetic field without the need of increasing the global temperature of the environment, proving the efficacy of the hot spot mechanism in magnetic-responsive drug delivery devices.

Mesoporous silica nanoparticles grafted with a light-responsive protein shell for highly cytotoxic antitumoral therapy

A novel phototriggered drug delivery nanocarrier, which exhibits very high tumor cytotoxicity against human tumoral cells, is presented. This device is based on mesoporous silica nanoparticles decorated with a biocompatible protein shell cleavable by light irradiation. The proteins that compose the protein shell (avidin, streptavidin and biotinylated transferrin) act as targeting and capping agents at the same time, avoiding the use of redundant systems. The light responsive behavior is provided by a biotinylated photocleavable cross-linker covalently grafted on the mesoporous surface, which suffers photocleavage by UV radiation (366 nm). Human tumoral cells incubated in the presence of a very low particle concentration enter into the apoptotic stage after a short irradiation time. Thus, the system described here could be applied to the treatment of exposed tumors that affect the skin, oesophagus, and stomach, among others, and are easily accessible for light irradiation.

Effect of surfactants on the performance of tubular and spherical micromotors – a comparative study

The development of artificial micromotors is one of the greatest challenges of modern nanotechnology. Even though many kinds of motors have been published in recent times, systematic studies on the influence of components of the fuel solution are widely missing. Therefore, the autonomous movement of Pt-microtubes and Pt-covered silica particles is comparatively observed in the presence and absence of surfactants in the medium. One representative of each of the three main surfactant classes - anionic (sodium dodecyl sulfate, SDS), cationic (benzalkonium chloride, BACl) and non-ionic (Triton X) - has been chosen and studied.

Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues

Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues.

In‐vivo behavior of Si‐hydroxyapatite/polycaprolactone/DMB scaffolds fabricated by 3D printing

Scaffolds made of polycaprolactone and nanocrystalline silicon-substituted hydroxyapatite have been fabricated by 3D printing rapid prototyping technique. To asses that the scaffolds fulfill the requirements to be considered for bone grafting applications, they were implanted in New Zealand rabbits. Histological and radiological studies have demonstrated that the scaffolds implanted in bone exhibited an excellent osteointegration without the interposition of fibrous tissue between bone and implants and without immune response after 4 months of implantation. In addition, we have evaluated the possibility of improving the scaffolds efficiency by incorporating demineralized bone matrix during the preparation by 3D printing. When demineralized bone matrix (DBM) is incorporated, the efficacy of the scaffolds is enhanced, as new bone formation occurs not only in the peripheral portions of the scaffolds but also within its pores after 4 months of implantation. This enhanced performance can be explained in terms of the osteoinductive properties of the DBM in the scaffolds, which have been assessed through the new bone tissue formation when the scaffolds are ectopically implanted.

Control of the electrochemical reduction of o-nitrophenol by pH imposition in acetonitrile

Abstract An electrochemical study using d.c. polarography, cyclic voltammetry and coulometry of o-nitrophenol has been performed in acetonitrile, in the presence of five buffer solutions of pH 20.0, 17.2, 16.2, 11.8 and 8.1. Using linear sweep voltammetry, it was found that at pH 20, the mechanism involves a reversible monoelectronic charge transfer in an Er mechanism. This is possible by avoiding the self-protonation reaction. At lower pH values, the mechanism involves a reversible monoelectronic charge transfer followed by protonation steps and homogeneous charge transfer due to disproportionation of the protonated intermediates. At pH 17.2 and 11.8, the mechanisms for the homogeneous charge transfer steps were found to be DISP2 type (disproportionation order two). At pH 16.2 and 8.1, mechanisms of the DISP1 or ECE type (disproportionation order one) are proposed. Coulometry experiments support the mechanisms proposed: at pH 20, − O θ NO 2 + 1 e − = − O θ NO 2 − , at pH 17.2, HO θ NO 2 + 2 e − + H + = HO θ NO 2 H − ; at pH 16.2, HO θ NO 2 2 e − + 2 H + = HO θ NO + H 2 O ; at pH 11.8, HO θ NO 2 + 3 e − + 3 H + = HO θ NOH + H 2 O ; and at pH 8.1, HO θ NO 2 + 4 e − + 4 H + = HO θ NHOH + H 2 O . From polarographic I/Io = f(pH) plots, it was possible to assign p K a , values to the acid-base pairs involved.

Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non‐viral Oligonucleotide Delivery Carriers

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability.

Thermoseeds for interstitial magnetic hyperthermia: from bioceramics to nanoparticles

The development of magnetic materials for interstitial hyperthermia treatment of cancer is an ever evolving research field which provides new alternatives to antitumoral therapies. The development of biocompatible magnetic materials has resulted in new biomaterials with multifunctional properties, which are able to adapt to the complex scenario of tumoral processes. Once implanted or injected in the body, magnetic materials can behave as thermoseeds under the effect of AC magnetic fields. Magnetic bioceramics aimed to treat bone tumors and magnetic nanoparticles are among the most studied thermoseeds, and supply different solutions for the different scenarios in cancerous processes. This paper reviews some of the biomaterials used for bone cancer treatment and skeletal reinforcing, as well as the more complex topic of magnetic nanoparticles for intracellular targeting and hyperthermia.