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As cell permeability of many anticancer drugs is expected to be poor, we are also interested in the attachment of membrane-interaction peptides to our scaffolds in order to assist in delivery. The peptides, derived from the Herpes Simplex Virus type 1 fusion proteins, allows the peptidodendrimer to penetrate into the cellular matrix mainly through a non-active translocation mechanism, whereas unfunctionalized dendrimers are excluded from translocation. Furthermore, the virally derived peptides render the peptidodendrimer an effective antiviral agent.
A fundamental limitation of current diagnostics and therapeutics is the lack of a single delivery system that has the potential to not only deliver therapeutics to the disease site of interest with high fidelity, i.e. target delivery, but also allows for diagnostics. We are engineering novel dendritic or dendrimer-polymer scaffolds with controlled architectures that utilize a targeting group, and present a drug and group(s) for imaging. We view that precise control of dendrimer design through the integration of orthogonal functionalization strategies will lead to a unique delivery platform for a wide variety of disease.
Our platforms are based on polyamide based dendrimers because they are based solely on a peptide-like backbone and have demonstrated low toxicities and non-immunogenicities. We have developed a synthesis scheme that combines up to three orthogonal functionalization strategies allowing for the formation of highly controlled multifunctional materials. Current efforts are targeted towards the attachment of drugs, targeting groups, imagining moieties, and/or membrane-interacting peptides on a single dendrimer or dendronized polymer.