Branched architectures with asymmetric polymeric arms provide an advantageous platform for the construction of tailored nanocarriers for therapeutic interventions. Simple and adaptable synthetic methodologies to amphiphilic miktoarm star polymers have been developed in which spatial location of reactive oxygen species (ROS) and glutathione (GSH) responsive entities is articulated to be on the corona shell surface or inside the core. The design of such architectures is facilitated through versatile building blocks and selected combinations of ring‐opening polymerization, Steglich esterification, and alkyne‐azide click reactions. Soft nanoparticles from aqueous self‐assembly of these stimuli responsive miktoarm stars have low critical micelle concentrations and high drug loading efficiencies. Partial corona shedding upon response to ROS is accompanied by an increase in drug release, without significant changes to overall micelle morphology. The location of the GSH responsive unit at the core leads to micelle disassembly and complete drug release. Curcumin loaded soft nanoparticles show higher efficiencies in preventing ROS generation in extracellular and cellular environments, and in ROS scavenging in human glioblastoma cells. The ease in synthetic elaboration and an understanding of structure‐property relationships in stimuli responsive nanoparticles offer a facile venue for well‐controlled drug delivery, based on the extra‐ and intracellular concentrations of ROS and GSH.
A simple one-pot methodology provides easy access to amphiphilic PEG–pyrrole backbone polymers, which self-assemble into soft nanoparticles enabling efficient drug loading/sustained release and can be detected inside cells.
Ultra-small gold nanoclusters are atomically precise structures that modulate organelles and redox-responsive transcription factors in human primary astrocytes.
The
purpose of the current study is to uncover the impact of small
liganded gold nanoclusters with 10 gold atoms and 10 glutathione ligands
(Au10SG10) on several biomarkers in human microglia.
We established the links connecting the atomically precise structure
of Au10SG10 with their properties and changes
in several biomolecules under oxidative stress. Au10SG10 caused the loss of mitochondrial metabolic activity, increased
lipid peroxidation and translocation of an alarmin molecule, high
mobility group box 1 (HMGB1), from the nucleus to the cytosol. Molecular
modeling provided an insight into the location of amino acid interaction
sites with Au10SG10 and the nature of bonds
participating in these interactions. We show that Au10SG10 can bind directly to the defined sites of reduced, oxidized,
and acetylated HMGB1. Further studies with similar complementary approaches
merging live-cell analyses, determination of biomarkers, and cell
functions could lead to optimized gold nanoclusters best suited for
diagnostic and bioimaging purposes in neuroscience.
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