Search Results
Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies
2021, Alghamdi, Majed, Gumbleton, Mark, Newland, Ben
Glioblastoma (GBM) is the most aggressive malignant brain tumor and is associated with a very poor prognosis. The standard treatment for newly diagnosed patients involves total tumor surgical resection (if possible), plus irradiation and adjuvant chemotherapy. Despite treatment, the prognosis is still poor, and the tumor often recurs within two centimeters of the original tumor. A promising approach to improving the efficacy of GBM therapeutics is to utilize biomaterials to deliver them locally at the tumor site. Local delivery to GBM offers several advantages over systemic administration, such as bypassing the blood-brain barrier and increasing the bioavailability of the therapeutic at the tumor site without causing systemic toxicity. Local delivery may also combat tumor recurrence by maintaining sufficient drug concentrations at and surrounding the original tumor area. Herein, we critically appraised the literature on local delivery systems based within the following categories: polymer-based implantable devices, polymeric injectable systems, and hydrogel drug delivery systems. We also discussed the negative effect of hypoxia on treatment strategies and how one might utilize local implantation of oxygen-generating biomaterials as an adjuvant to enhance current therapeutic strategies. © 2021 The Royal Society of Chemistry.
Hydration of nitriles using a metal-ligand cooperative ruthenium pincer catalyst
2019, Guo, Beibei, de Vries, Johannes G., Otten, Edwin
Nitrile hydration provides access to amides that are important structural elements in organic chemistry. Here we report catalytic nitrile hydration using ruthenium catalysts based on a pincer scaffold with a dearomatized pyridine backbone. These complexes catalyze the nucleophilic addition of H2O to a wide variety of aliphatic and (hetero)aromatic nitriles in tBuOH as solvent. Reactions occur under mild conditions (room temperature) in the absence of additives. A mechanism for nitrile hydration is proposed that is initiated by metal-ligand cooperative binding of the nitrile. This journal is © The Royal Society of Chemistry.
Influence of nanobody binding on fluorescence emission, mobility, and organization of GFP-tagged proteins
2020, Schneider, Falk, Sych, Taras, Eggeling, Christian, Sezgin, Erdinc
Advanced fluorescence microscopy studies require specific and monovalent molecular labeling with bright and photostable fluorophores. This necessity led to the widespread use of fluorescently labeled nanobodies against commonly employed fluorescent proteins (FPs). However, very little is known how these nanobodies influence their target molecules. Here, we tested commercially available nanobodies and observed clear changes of the fluorescence properties, mobility and organization of green fluorescent protein (GFP) tagged proteins after labeling with the anti-GFP nanobody. Intriguingly, we did not observe any co-diffusion of fluorescently labeled nanobodies with the GFP-labeled proteins. Our results suggest significant binding of the nanobodies to a non-emissive, likely oligomerized, form of the FPs, promoting disassembly into monomeric form after binding. Our findings have significant implications on the application of nanobodies and GFP labeling for studying dynamic and quantitative protein organization in the plasma membrane of living cells using advanced imaging techniques.