Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers

The encapsulation and selective delivery of therapeutic compounds within polymeric nanoparticles offers hope for the treatment of a variety of diseases. Traditional approaches to trigger selective cargo release typically rely on polymer degradation which is not always sensitive to the biological location of a material. In this report, we prepare nanoparticles from thermoresponsive polymers with a ‘solubility release catch’ at the chain-end. This release catch is exclusively activated in the presence of intracellular glutathione, triggering an ‘isothermal’ response and promoting a change in polymer solubility. This solubility switch leads to specific and rapid nanoparticle disassembly, release of encapsulated cargo and produces completely soluble polymeric side-products

Dual effect of thiol addition on fluorescent polymeric micelles: ON-to-OFF emissive switch and morphology transition

YesThe morphology transition from micelles to vesicles of a solution-state self-assembled block copolymer, containing a fluorescent dye at the core–shell interface, has been induced by an addition–elimination reaction using a thiol, and has been shown to be coupled to a simultaneous ON-to-OFF switch in particle fluorescence.EPSRC and the IAS at the University of Warwic

Chemical specificity in REDOX-responsive materials:the diverse effects of different Reactive Oxygen Species (ROS) on polysulfide nanoparticles

REDOX responsive (nano)materials typically exhibit chemical changes in response to the presence and concentration of oxidants/reductants. Due to the complexity of biological environments, it is critical to ascertain whether the chemical response may depend on the chemical details of the stimulus, in addition to its REDOX potential, and whether chemically different responses can determine a different overall performance of the material. Here, we have used oxidation-sensitive materials, although these considerations can be extended also to reducible ones. In particular, we have used poly(propylene sulfide) (PPS) nanoparticles coated with a PEGylated emulsifier (Pluronic F127); inter alia, we here present also an improved preparative method. The nanoparticles were exposed to two Reactive Oxygen Species (ROS) typically encountered in inflammatory reactions, hydrogen peroxide (H2O2) and hypochlorite (ClO−); their response was evaluated with a variety of techniques, including diffusion NMR spectroscopy that allowed to separately characterize the chemically different colloidal species produced. The two oxidants triggered a different chemical response: H2O2 converted sulfides to sulfoxides, while ClO− partially oxidized them further to sulfones. The different chemistry correlated to a different material response: H2O2 increased the polarity of the nanoparticles, causing them to swell in water and to release the surface PEGylated emulsifier; the uncoated oxidized particles still exhibited very low toxicity. On the contrary, ClO− rapidly converted the nanoparticles into water-soluble, depolymerized fragments with a significantly higher toxicity. The take-home message is that it is more correct to discuss ‘smart’ materials in terms of an environmentally specific response to (REDOX) stimuli. Far from being a problem, this could open the way to more sophisticated and precisely targeted applications

Amphiphilic Polymer Assemblies Responsive To Chemical, Physical, And Biological Stimuli

The applications of stimuli responsive materials have tremendously increased over the past decade. In particular, these materials can potentially be used for improving the selectivity and efficiency of delivering a payload (drug) in drug delivery applications. This thesis discusses the design and synthesis of amphiphilic polymers which can respond to chemical, physical, and biological stimuli. We have synthesized a novel amphiphilic block copolymer which can form micellar assemblies in aqueous medium and respond to multiple stimuli; viz physical (temperarure) and chemical (pH, DTT and gluthathione). This amphiphilic block copolymer is sensitive not only to a single stimulus, but also to the simultaneous presence of multiple stimuli. This system provides a unique opportunity to fine tune the release kinetics of the encapsulated hydrophobic guest molecules. Besides designing polymeric systems responsive to chemical and physical stimuli, we were also interested in systems responsive to biological stimuli, since they can directly respond to the primary imbalances in biological functions instead of a secondary change such as pH, or redox potential characteristics. Amphiphilic polymers designed earlier in the group with -COOH as the hydrophilic group are known to provide micellar assemblies in water. The charged exterior (-COO - ) of the micellar assemblies was used to disrupt protein-protein interaction. To further investigate if these polymeric micelles can be made responsive to proteins, we have studied the binding event of a ligand (pendant on the polymer chain) with the protein. Block copolymers and random copolymers functionalized with specific ligands were used as model systems to understand the interaction of polymers with proteins. We established that block copolymers provide better binding with proteins compared to random copolymers, possibly due to the higher effective molarity of ligands present in the former than the latter. Amphiphilic biaryl dendrimers decorated with ligands at different locations were also studied. We established that ligands present in at any layer of the dendron are equally available for binding with protein. Amphiphilic homopolymer and amphiphilic biaryl dendrimer were found to be the potential candidates for drug delivery applications by using proteins as the trigger to disassemble the micelles