Benzoic acid, acetylsalicylic acid, and 4‐acetamidobenzoic acid have been covalently linked by ester bonds to α,β‐poly(N‐hydroxyethyl)‐DL‐aspartamide (PHEA), a water soluble and nontoxic polymer, in order to study PHEA as a drug carrier.
Carbon nanodots are known for their appealing optical properties, especially their intense fluorescence tunable in the visible range. However, they are often affected by considerable issues of optical and structural heterogeneity, which limit their optical performance and limit the practical possibility of applying these nanoparticles in several fields.Here we developed a synthesis method capable of producing a unique variety of carbon nanodots displaying an extremely high visible absorption strength (ε > 3 × 10 6 M(dot) −1 cm −1 ) and a high fluorescence quantum yield (73%). The high homogeneity of these dots reflects in many domains: morphological (narrow size distribution), structural (quasiperfect nanocrystals with large electronic bandgaps), and optical (nontunable fluorescence from a single electronic transition). Moreover, we provide the proof of principle that an aqueous solution of these dots can be used as an active medium in a laser cavity, displaying a very efficient laser emission with dye-like characteristics, which reflects the benefits of such a highly homogeneous type of carbon-based nanodots.
Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide-polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative ζ potential, and biocompatibility toward human bronchial epithelial cells. The high surface poly(ethylene glycol) density of fluorescent nanoparticles and poly(ethylene glycol) brush-like conformation assumed on their surface, conferred to pegylated nanoparticles the mucus-penetrating properties, properly demonstrated by assessing their ability to avoid interactions with mucus components and to penetrate cystic fibrosis artificial mucus. Finally, ibuprofen release profile and uptake capacity within human bronchial epithelial cells in the presence of cystic fibrosis artificial mucus showed how these mucus-penetrating nanoparticles could rapidly diffuse through the mucus barrier reaching the mucosal surface, where they could offer a sustained delivery of ibuprofen at the site of disease.
Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with aminederivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.
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