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Nanotechnology enables the creation of delivery vehicles able to overcome physiologically imposed barriers, allowing new approaches for reducing the unwanted side effects of systemic delivery of drug, increasing targeting efficiency and so improving therapy efficacy. Owing to the considerable advances in material sciences and pharmaceutics, a broad range of different inorganic or organic drug nanocarriers have been developed. Furthermore, researchers have shown that the combination of inorganic and organic chemistries in one single material, named metal-organic framework (MOF), offers structural designability at the molecular level together with tunable porosity and chemical functionalisability. While the MOF size can be controlled at the nanometer scale, these features are of paramount interest in the development of the next generation of drug delivery systems. After a short state-of-the-art about MOF technology and within the drug delivery context, this paper discusses the benefits of using MOF nanoparticles compared to dendrimers and mesoporous silica nanoparticles in order to understand the challenges that must still be overcome. [ABSTRACT FROM AUTHOR]

The synthesis of microcapsules consisting of DNA shells crosslinked by anti-VEGF (vascular epithelial growth factor) or anti-ATP (adenosine triphosphate) aptamers and loaded with tetramethylrhodamine-modified dextran, TMR-D, and Texas Red-modified dextran, TR-D, respectively, as fluorescence labels acting as models for drug loads, is described. The aptamer-functionalized microcapsules act as stimuli-responsive carriers for the triggered release of the fluorescent labels in the presence of the overexpressed cancer cell biomarkers VEGF or ATP. The VEGF- and ATP-responsive microcapsules are, also, loaded with the anticancer drug doxorubicin (DOX), in the form of DOX-functionalized dextran, DOX-D. The release of DOX-D from the respective microcapsules proceeds in the presence of VEGF or ATP as triggers. Preliminary cell experiments reveal that the ATP-responsive DOX-D-loaded microcapsules undergo effective endocytosis into MDA-MB-231 cancer cells. The ATP-responsive DOX-D-loaded microcapsules incorporated into the MDA-MB-231 cancer cells reveal impressive cytotoxicity as compared to normal epithelial MCF-10A breast cells (50% vs 0% cell death after 24 h, respectively). The cytotoxicity of the ATP-responsive DOX-D-loaded microcapsules toward the cancer cells is attributed to the effective unlocking of the microcapsules by overexpressed ATP, and to the subsequent release of DOX from the dextran backbone under acidic conditions present in cancer cells (pH = 6.2). [ABSTRACT FROM AUTHOR]

Engineering the physical properties of particles, especially their size, is an important parameter in the fabrication of successful carrier systems for the delivery of therapeutics. Here, various routes were explored for the fabrication of particles in the nanosize regime. It was demonstrated that the use of a charged species and/or solvent with high dielectric constant can influence the size and distribution of particles, with the charged species having a greater effect on the size of the particles and the solvent a greater effect on the distribution of the particles. In addition to the fabrication of nanoparticles, their fractionation into specific size ranges using centrifugation was also investigated. The in vitro particle uptake and intracellular transport of these nanoparticles was studied as a function of size and incubation period. The highest level of intralysosomal localization was observed for the smallest nanoparticle group (average of 174 nm), followed by the groups with increasing sizes (averages of 378 and 575 nm), most likely due to the faster endosomal uptake of smaller particles. In addition, the internalization of nanoparticle clusters and number of nanoparticles per cell increased with longer incubation periods. This work establishes a technological approach to compartmentalized nanoparticles with defined sizes. This is especially important as relatively subtle differences in size can modulate cell uptake and determine intercellular fate. Future work will need to address the role of specific targeting ligands on cellular uptake and intracellular transport of compartmentalized nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: Arguably targeting is one of the biggest problems for controlled drug delivery. In the case that drugs can be directed with high efficiency to the target tissue, side effects of medication are drastically reduced. Colloidal inorganic nanoparticles (NPs) have been proposed and described in the last 10years as new platforms for in vivo delivery. However, though NPs can introduce plentiful functional properties (such as controlled destruction of tissue by local heating or local generation of free radicals), targeting remains an issue of intense research efforts. While passive targeting of NPs has been reported (the so-called enhanced permeation and retention, EPR effect), still improved active targeting would be highly desirable. One classical approach for active targeting is mediated by molecular recognition via capture molecules, i.e. antibodies (Abs) specific for the target. In order to apply this strategy for NPs, they need to be conjugated with Abs against specific biomarkers. Though many approaches have been reported in this direction, the controlled bioconjugation of NPs is still a challenge. In this article the strategies of controlled bioconjugation of NPs will be reviewed giving particular emphasis to the following questions: 1) how can the number of capture molecules per NP be precisely adjusted, and 2) how can the Abs be attached to NP surfaces in an oriented way. Solution of both questions is a cornerstone in controlled targeting of the inorganic NPs bioconjugates. [Copyright &y& Elsevier]

Abstract: Polymeric multilayer capsules have emerged as a novel drug delivery platform. These capsules are fabricated through layer-by-layer sequential deposition of polymers onto a sacrificial core template followed by the decomposition of this core yielding hollow capsules. The resulting nanometer thin membrane is permselective, allowing diffusion of water and ions but excluding larger molecules. Moreover, the sequential fabrication procedure allows a precise fine-tuning of the capsules’ physicochemical and biological properties. These properties have put polymeric multilayer capsules under major attention in the field of drug delivery. In this review we focus on polymeric multilayer capsule mediated delivery of biotechnological macromolecular drugs such as peptides, proteins and nucleic acids. [Copyright &y& Elsevier]

The role of PEG-coated gold nanoparticles (Au NPs) on the anti-proliferative effect of Specific Nutrient Synergy (SNS) on HTLV-1 infected (C91-PL and HuT-102) and non-infected (CEM and Jurkat) malignant T-lymphocytes cells, was investigated. When PEG-coated Au NPs (of different molecular weights) were added alone, there was no effect on either viability or proliferation of the leukemic cell lines studied. Treatment of cells with SNS and PEG (5 or 10 kDa) coated Au NP reduced significantly the proliferation in all cell lines tested; this reached more than 50% reduction as compared to the control for cells treated for 96 h. Data showed that the best anti-proliferative effect was obtained using SNS and Au NP coated with PEG of molecular weights of 5 and 10 kDa with almost no effect of PEG of lower molecular weights (0.75 and 2 kDa) or higher ones (20 kDa). This was true as well for HTLV-1 infected as for non-infected malignant T-lymphocytes. Electron microscopy results showed uptake of the gold particles to Jurkat cells. All described effects are specific to leukemia cell lines, and no effects were observed with freshly activated human mononuclear lymphocytes as control. [ABSTRACT FROM AUTHOR]

Adenosine triphosphate (ATP)–responsive DNA‐based microcapsules loaded with the chemotherapeutic doxorubicin drug are synthesized and incorporated into cancer cells. I. Willner and co‐workers find, on page 4262, that over‐expressed ATP in cancer cells dissociates the microcapsules and releases the drug, resulting in selective cytotoxicity toward cancer cells. [ABSTRACT FROM AUTHOR]