Viral Peptide Targeted Delivery of Nano-Therapeutics

Over the past decade, an increasing number of potential drugs have been suggested for therapeutic applications. Often bio-macromolecules show a limited ability to cross the plasma membrane resulting in poor cellular access, which largely prevents them from reaching intracellular targets and from crossing epithelial or endothelial barriers. Moreover, neurological disorders contribute significantly to the global burden of disease and are likely to increase in the coming years due to an aging population; however, significant efforts have been devoted towards the development of improved therapies for central nervous system (CNS) diseases, treatments remain limited due to the inability of therapeutic agents to effectively cross the blood-brain-barrier (BBB).[1] The development of nanotechnology provides powerful tools to deliver therapeutics to target sites. This presentation targets major advances in the design and realization of nano-scaffolds for theranostics. 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 and cell delivery, i.e. cell penetration and uptake and thus the obtainment of a toolbox that combines targeting and delivery with imaging and targeted cell uptake. The discovery of several peptides with the ability to cross the plasma membrane of eukaryotic cells by a possibly receptor- and endocytosis-independent mechanism, has opened a new avenue in biomedical research. Among the so-called cell penetrating peptides (CPPs), Tat, penetratin and VP22 have been widely used and have shown to be entrapped in intracellular organelles. Thus, one of the main goals of recent research is the obtainment of novel delivery systems that are able to cross membranes without being entrapped in intracellular organelles[2]. Viral derived peptides, and in particular those derived by viral entry proteins, may be useful as delivery vehicles due to their intrinsic properties of inducing membrane perturbation. The present talk will describe results obtained with the use of a peptide derived from Herpes simplex virus type 1 for the delivery of bioactive molecules or fluorescent dyes inside the host cell. In particular, its use for the intracellular delivery of quantum dots (QDs), liposomes, dendrimers and nanoparticles will be addressed.