RESUMEN
We present the synthesis of amorphous, mesoporous, colloidal magnesium phosphate-citrate nanoparticles (MPCs) from biogenic precursors, resulting in a biocompatible and biodegradable nanocarrier that amplifies the action of the anticancer drug methotrexate (MTX). Synthesis conditions were gradually tuned to investigate the influence of the chelating agent citric acid on the colloidal stability and the mesoporosity of the obtained nanoparticles. With optimized synthesis conditions, a large BET surface area of 560 m2/g was achieved. We demonstrate the potential of these biocompatible and biodegradable mesoporous MPCs as a drug delivery system. Lipid-coated MPCs were used to load the fluorescent dye calcein and the chemotherapeutic agent MTX into the mesopores. In vitro experiments show very low premature release of the cargo but efficient stimuli-responsive release in an environment of pH 5.5, in which MPCs degrade. Lipid-coated MPCs are taken up by cancer cells and are nontoxic up to concentrations of 100 µg/mL. When loaded with MTX serving as a representative model drug for in vitro studies, MPCs induced efficient cell death with an IC50 value of 1.1 µg/mL. Compared to free MTX, its delivery with MPCs enhances its efficiency by an order of magnitude. In summary, we have developed a biodegradable nanomaterial synthesized from biocompatible precursors that are neither toxic by themselves nor in the form of nanoparticles. With these features, MPCs may be applied as drug delivery systems and have the potential to reduce the side effects of current chemotherapies.
Asunto(s)
Antineoplásicos , Nanopartículas , Antineoplásicos/farmacología , Ácido Cítrico , Portadores de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Células HeLa , Humanos , Lípidos , Compuestos de Magnesio , Metotrexato/farmacología , Fosfatos , Dióxido de SilicioRESUMEN
Mesoporous nanoparticles for drug delivery would benefit significantly from further improvements in targeting efficiency and endosomal release. We present a system based on colloidal mesoporous silica nanoparticles with targeting-ligands and a red-light photosensitizer. This nanoparticle system provides spatial and temporal control of the release of drugs into the cytosol of cancer cells. Furthermore, the system presents a general platform since it can be loaded with different cargos and adapted for targeting of multiple cell types.
Asunto(s)
Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos , Nanopartículas , Neoplasias/tratamiento farmacológico , Dióxido de Silicio/química , Antineoplásicos/administración & dosificación , HumanosRESUMEN
Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the development of precisely controllable and highly modular theranostic systems.