Porous Metal–Organic Framework Nanoparticles

Metal–organic frameworks (MOFs) are hybrid crystalline particles composed of metal cations and organic linkers. Ranging from micro- to nanoscale depending on the preparation conditions, they have achieved a prevalent position among porous materials. The fact that varying either the metal cation or the organic component leads to a wide range of pore sizes and structures has made them very appealing materials in a broad variety of fields, including gas storage, heterogeneus catalysis, separation, imaging, biosensing, agriculture, and biomedicine. By optimizing the internal pore volume, many molecules of different natures can be accommodated within the matrix. For instance, the anticancer drug doxorubicin is well known to enter within iron trimesate MIL-100(Fe) nanoMOF. However, the use of this inclusion complex in biomedicine requires the controlled release of the drug. As reported in one of the articles within this Special Issue [1], this goal can be achieved either by modifying the way the drug is loaded into the MOF or by noncovalently coating the surface with appropriate biocompatible materials. Furthermore, the latter can also lead to a higher colloidal stability of the particles. The innovative use of the ssNMR technique on these inclusion complexes associated with a selective isotope labeling strategy gave the authors deeper insights into both the structure of the complexes as well as to the drug release rates and mechanism

Glycoclusters and their applications as anti-infective agents, vaccines and targeted drug delivery systems

This chapter reviews the most relevant and recent reports on the applications of glycoclusters as inhibitors and antiadhesive agents against bacteria and viruses, synthetic vaccines, and site-specific drug and gene delivery systems. A common strategy to achieve these goals is the targeting of carbohydrate-binding proteins (lectins) present on the surface of pathogens and tumor cells. Such target lectins are typically involved in cell recognition, signaling, and adhesion or are overexpressed in cell proliferation and tumor development. Multivalency is crucial for the enhancement of such carbohydrate-protein interactions, which are otherwise too weak in biological terms for such applications. In addition, size and spatial arrangement matching between the glycocluster and the biological target is important to obtain a high binding affinity in many cases. A large number of different scaffolds have been used for building such multivalent structures, including cyclodextrins, calixarenes, oligo- and cyclooligopeptides, pentacyclen, pentaerythritol, and saccharides, among others, giving rise to an enormous variety of modes of carbohydrate display with different topologies and valencies

Cyclodextrin-Modified Inorganic Materials for the Construction of Nanocarriers

Inorganic nanoparticles, such as gold, silver, quantum dots and magnetic nanoparticles, offer a promising way to develop multifunctional nanoparticles for biomedical applications. Such nanoparticles have the potential to combine in a single, stable construct various functionalities, simultaneously providing imaging abilities, thermal therapies and the ability to deliver drugs in a targeted fashion. An approach for providing drug loading abilities to these inorganic nanoparticles consists in the modification of their surface with a coating of cyclodextrins, and thereby endowing the nanoparticles with the potential of functioning as drug nanocarriers. This review presents the advances carried out in the preparation of cyclodextrin-contained gold, silver, quantum dot and magnetic nanoparticles as well as their applications as drug nanocarriers. The nanoparticle surface can be modified incorporating cyclodextrin moieties, (i) in situ during the synthesis of the nanoparticles, either using the cyclodextrin as reducing agent or as stabilizer; or (ii) in a post-synthetic stage. The cyclodextrin coating contributes to provide biocompatibility to the nanoparticles and to reduce their cytotoxicity. Cyclodextrin-modified nanoparticles display a multivalent presentation of quasi-hydrophobic cavities that enables, not only drug loading in a non-covalent manner, but also the non-covalent assembly of targeting motifs and optical probes. This paper also provides an overview of some of the reported applications including the in vitro studies and, to a lesser extent, in vivo studies on the drug-loaded nanoparticles behavior

Electrochemical detection of glutathione S-transferase: An important enzyme in the cell protective mechanism against oxidative stress

Oxidative stress arises when the antioxidant capacity of cells to clean the excess production of reactive oxygen species (ROS) decreases. Several human diseases seem to be related with an increment in the oxidative stress. In this regard, GSH present in the cells works by neutralizing ROS and other xenobiotics through the glutathione S-transferase (GST) enzyme. Thus, the level of expression of GST is an important factor in determining the sensitivity of cells to toxic chemicals or xenobiotic compounds. Therefore, the detection of GST levels is fundamental in the clinical diagnosis of ROS-related diseases. Here, we describe a methodology, based on the voltammetric properties of the ferrocene group (used as electrochemical probe), which can be applied for selective detection of GST levels in human cells. The electrochemical signal measured is associated to the specific interaction of a ferrocenyl-GSH derivate with the G- and H-sites of this enzyme

Binding ability properties of β-cyclodextrin dimers linked through their secondary faces towards cancer chemotherapeutic agent methotrexate

The binding ability properties of two β-cyclodextrin dimers linked through their secondary faces by short, rigid spacer arms towards the cancer chemotherapeutic agent methotrexate were studied by ITC and NMR (1D and ROESY) experiments. Both dimers are able to bind two molecules of methotrexate with a binding constant between 2.4 and 3.5 times higher than that for native β-cyclodextrin, the dimer having the shortest linker forming the most stable complex

A Practical, Large-Scale Synthesis of Pyrene-2-Carboxylic Acid

Pyrene-2-carboxylic acid is a versatile intermediate for introducing the unusual 2-pyrenyl unit into functional organic molecules. A classical preparation for this molecule has been revised and improved to give a robust and efficient three-step process. The method has been applied on a multigram scale to give pyrene-2-carboxylic acid in >70% overall yield from pyrene

Facile synthesis of per(6-O-tert-butyldimethylsilyl)-α-, β-, and γ-cyclodextrin as protected intermediates for the functionalization of the secondary face of the macrocycles

Per(6-O-tert-butyldimethylsilyl)-α-, β- and γ-cyclodextrin derivatives are well-known as synthetic intermediates that enable the selective mono-, partial, or perfunctionalization of the secondary face of the macrocycles. Although silylation of the primary rim is readily achieved by treatment with tert-butyldimethylsilyl chloride in the presence of pyridine (either alone or mixed with a co-solvent), the reaction typically results in a mixture containing both under- and oversilylated byproducts that are difficult to remove. To address this challenge in preparing a pure product in high yield, we describe an approach that centers on the addition of a controlled excess of silylating agent to avoid the presence of undersilylated species, followed by the removal of oversilylated species by column chromatography elution with carefully designed solvent mixtures. This methodology works well for 6-, 7-, and 8-member rings (α-, β-, and γ-cyclodextrins, respectively) and has enabled us to repeatedly prepare up to ⁓35 g of ≥98% pure product (as determined by HPLC) in 3 d. We also provide procedures for lower-scale reactions, as well as an example of how the β-cyclodextrin derivative can be used for functionalization of the secondary face of the molecule

A non‐covalent “click chemistry” strategy to efficiently coat highly porous MOF nanoparticles with a stable polymeric shell

Background Metal-organic framework nanoparticles (nanoMOFs) are biodegradable highly porous materials with a remarkable ability to load therapeutic agents with a wide range of physico-chemical properties. Engineering the nanoMOFs surface may provide nanoparticles with higher stability, controlled release, and targeting abilities. Designing postsynthetic, non-covalent self-assembling shells for nanoMOFs is especially appealing due to their simplicity, versatility, absence of toxic byproducts and minimum impact on the original host-guest ability. Methods In this study, several β-cyclodextrin-based monomers and polymers appended with mannose or rhodamine were randomly phosphorylated, and tested as self-assembling coating building blocks for iron trimesate MIL-100(Fe) nanoMOFs. The shell formation and stability were studied by isothermal titration calorimetry (ITC), spectrofluorometry and confocal imaging. The effect of the coating on tritium-labeled AZT-PT drug release was estimated by scintillation counting. Results Shell formation was conveniently achieved by soaking the nanoparticles in self-assembling agent aqueous solutions. The grafted phosphate moieties enabled a firm anchorage of the coating to the nanoMOFs. Coating stability was directly related to the density of grafted phosphate groups, and did not alter nanoMOFs morphology or drug release kinetics. Conclusion An easy, fast and reproducible non-covalent functionalization of MIL-100(Fe) nanoMOFs surface based on the interaction between phosphate groups appended to β-cyclodextrin derivatives and iron(III) atoms is presented. General significance This study proved that discrete and polymeric phosphate β-cyclodextrin derivatives can conform non-covalent shells on iron(III)-based nanoMOFs. The flexibility of the β-cyclodextrin to be decorated with different motifs open the way towards nanoMOFs modifications for drug delivery, catalysis, separation, imaging and sensing. This article is part of a Special Issue entitled “Recent Advances in Bionanomaterials” Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader

β‑Cyclodextrin-Bearing Gold Glyconanoparticles for the Development of Site Specific Drug Delivery Systems

Three novel gold nanoparticles containing multiple long, flexible linkers decorated with lactose, β-cyclodextrin and both simultaneously have been prepared. The interaction of such nanoparticles with β-D-galactose-recognizing lectins peanut agglutinin (PNA) and human galectin-3 (Gal-3) was demonstrated by UV-Vis studies. Gal-3 is well-known to be overexpressed in several human tumors and can act as biorecognizable target. This technique also allowed us to estimate their loading capability toward the anticancer drug methotrexate (MTX). Both results make these glyconanoparticles potential site-specific delivery systems for anticancer drugs

Quantum dot/cyclodextrin supramolecular systems based on efficient molecular recognition and their use for sensing

A supramolecular system based on ketoprofen functionalised CdSe/ZnS nanoparticles and pyrene-modified β-CD was prepared and successfully used for molecular sensing of different analytes. In addition, a strategy for the individual recovery of all the components of the sensing assay is reported