Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.

Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.

The beginnings of metal-organic frameworks (MOF) chemistry were established by Yaghi et al., in the 1990s. They started a new promising field for which, depending on the nature of the organic functionality and metal−ligand coordination chemistry, diversity of MOFs in terms of their structures and chemical properties is virtually endless. Since the 1990s it has been reported different synthetic routes (e.g., hydro-solvothermal synthesis, microwave and ultrasound-assisted synthesis, mechanochemistry, microemulsion synthesis, and continuous flow production). Nevertheless, no control on the shape and size of the crystal was achieved in a proper way. The results obtained during this work demonstrates that the surfactant plays an important role in the MOF´s synthesis protocol, in particular, in those with zeolitic imidazolate framework (ZIF-8) structure, by changing the former physico-chemical properties without altering their crystalline structure. That is, variations on surfactant´s properties lead to changes both in shape and size of MOFs without altering their intrinsic properties. Thus, this work is focused on the effect of two surfactants: sodium dodecyl sulfate (SDS) and hexadecyltrimethylammonium bromide (CTAB). In this sense, for each family of surfactant the influence of the surfactant tail chain length and the nature of their head group were investigated. For these studies, dynamic laser-light scattering (DLS), scanning electron microscopy (SEM) and powder X-ray diffraction (PXRD) were performed in order to characterize the physicochemical properties and the morphology of the obtained MOFs.

During the last few years, metal–organic frameworks (MOFs) are being considered as ideal candidates to find more efficient systems for the production and storage of energy