Enzyme-responisve PEG-dendron hybrids
Stimuli-responsive nanocarriers that can disassemble to release their encapsulated cargo upon external stimuli have gained increasing attention due to their possible utilization as smart drug delivery systems. Among the various types of stimuli, enzymes offer great potential for the activation of biomedical carriers due to their overexpression in various diseases. The design of enzyme-responsive block copolymers is highly challenging, as the enzyme must reach the enzyme-sensitive moieties, which are spread along the backbone of the polymer and might be hidden inside the hydrophobic cores of the self-assembled structures. The polydispersity of the stimuli-responsive block raises another significant challenge for the kinetic analysis and mechanistic study of the enzymatic response as the enzyme can have very different accessibility to the enzymatically activated moieties depending on their location along the polymer backbone, the length of the polymer chain, and its solubility. To address these challenges, we are developing highly modular polymeric platforms based on amphiphilic PEG-dendron hybrids. These amphiphilic hybrids can self-assemble in water into micellar nanocontainers that disassembled and released encapsulated molecular cargo upon enzymatic activation. The modularity of these PEG-dendron hybrids offers great control and tuning of the disassembly rate of the formed micelles by simple adjustment of the PEG length. Such smart amphiphilic hybrids could open the way for the fabrication of nanocarriers with tunable release rates for delivery applications.
From Empirical to Programmed Self-assembly
Complex nanoscale devices hold huge promise in many fields, ranging from smart drug delivery systems to electronics. Due to the difficulties of precisely controlling structures in the nanoscale with current top-down technologies, such device should be based on self-assembly of its different components. This bottom-up approach requires the design of building blocks that allow control over the shape, internal architecture and function of their supramolecular assemblies. We are interested in the hybridization of structural elements with block copolymers to yield self-organizing building blocks as a gateway to a large array of highly ordered and complex architectures that are currently not accessible. The ability to design and synthesize such building blocks will open the way for the development of new materials with tunable properties for a variety of applications ranging from manufacturing of semiconductors to medical imaging.
To address the need for nano-carriers for imaging and selective drug delivery applications we are interested in developing polymer based building blocks that can self-assemble in a programmed manner into functional assemblies. These polymeric platforms are designed to carry multiple types of drugs or imaging probes and moreover to allow control over the release rate of the cargo molecules from the nano-carrier.
Multifunctional Dendritic and Polymeric Platforms
Dendrimers are very attractive scaffolds for the delivery of therapeutics and/or diagnostic probes, with the two major approaches of loading being: encapsulation and functionalization of the chain ends. While both approaches seem to be promising they suffer from drawbacks due to the limited amount of cargo molecules and control over the stability of the loaded carriers. Therefore, we are looking into the development of novel strategies that provides internal reactive groups that are orthogonal to the moieties at the chain ends using a combination click chemistries. These new hybrid dendritic–linear delivery systems offer significant advantages in terms of loading capacity, stability and biocompatibility.
Confocal fluorescence microscopy images of live cells, show the internalization of the dendrimers (in red) and the release of the cargo (coumarin in blue) into the cytoplasm.