Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due to implications in therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, in which the kinetics of guest molecule release can be fine-tuned by control over cross-linking density. The polymer nanogel precursor is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. By introducing variations into the precursor polymer, such as molecular weight and the relative percentages of hydrophilic OEG units and hydrophobic PDS functionalities, we have achieved significant control over nanogel size. We show that the noncovalently encapsulated guest molecules can be released in response to a redox trigger, glutathione (GSH). Stability of dye encapsulation inside the nanogels and tunability in the release of guest molecules have been demonstrated through in vitro fluorescence resonance energy transfer (FRET) experiments. We show in vitro doxorubicin delivery into breast cancer cells (MCF-7) with nanogels of different cross-linking density to demonstrate that it plays a key role in the stable encapsulation of hydrophobic drug molecules and the cell-uptake efficiencies.
The stability of encapsulation in self-assembly systems is limited during blood circulation because of a requisite concentration for assembly formation. For deliberate molecular design for stable encapsulation, targeting, and triggered release, we have developed a facile synthetic method for highly stable, polymeric nanogels using a simple intra/interchain cross-linking reaction. We show a simple, emulsion-free method for the preparation of biocompatible nanogels that provides the ability to encapsulate hydrophobic guest molecules and surface functionalization which has potential for targeted delivery. We show that the noncovalently encapsulated guest molecules can be released in response to a biologically relevant stimulus.
One of the most fascinating subjects in areas such as nanoscience and biomimetic chemistry is concerned with the construction of novel supramolecular nanoscopic architectures with well defined shapes and functions. Supramolecular assemblies of aromatic rod molecules provide a facile entry into this area. Aromatic rigid rod molecules consisting of hydrophilic flexible chains, in aqueous solution can self-assemble into a variety of supramolecular structures through mutual interactions between aromatic rod molecules and water, including hydrophobic and hydrophilic interactions and pi-pi interaction. The supramolecular architecture in water can be manipulated by variation of the shape of the rigid segments, as well as the relative volume fraction of the flexible segment. The rigid aromatic segments have significant photonic and electronic properties. The self-assembly of aromatic rod molecules in water, therefore, can provide a strategy for the construction of well-defined and stable nanometer-size structures with chemical functionalities and physical properties as advanced materials for photonic, electronic and biological applications.
Exchange dynamics of lipophilic guest molecules, encapsulated in supramolecular nanoassemblies in aqueous solutions, have implications in evaluating the stability of drug delivery vehicle. This is because exchange dynamics is related to the propensity of a nanocarrier to be leaky. We describe a fluorescence resonance energy transfer (FRET) based method to evaluate guest exchange dynamics in the aqueous phase. We have utilized this method to analyze the stability of encapsulation in polymeric nanogels and other related amphiphilic nanoassemblies.
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