Vesicular nanostructures have garnered huge interest due to their great flexibility as drug carriers. Their structure allows for the simultaneous encapsulation of hydrophilic molecules within the aqueous core and hydrophobic compounds within the bilayer membrane. Polymeric vesicles, known as polymersomes, have been proposed as a drug delivery system for several decades because of their robust membrane and versatile chemistry. However, the use of synthetic polymers can lead to biocompatibility issues, such as the production of toxic metabolites or induction of an immune response. In contrast, polypeptides offer the potential to be fully biocompatible and biodegradable while retaining most of the advantageous properties of synthetic polymers. Polyhistidine is of particular interest in this regard due to its ionizable imidazole side group with a pKa of 6.0. As such, polyhistidine transitions from hydrophobic at neutral pH to hydrophilic at slightly acidic pH, making it the perfect candidate for a dissociable pH-sensitive vesicle membrane. To this end, we propose the use of histidine-based block copolypeptides to form peptidic vesicles capable of encapsulation and drug delivery. Amphiphilic histidine-based copolypeptides have been synthesized and self-assembled to produce ordered nanostructures. Self-assembly via pH switch demonstrates pH-sensitivity at a physiologically relevant pH, in addition to the formation of spherical nanostructures as seen with dynamic light scattering measurements and transmission electron microscopy imaging. The hydrophilic block has been designed to prevent protein fouling on the surface of the nanostructures. N-terminal modifications result in a hydrophobic block devoid of unwanted electrostatic interactions, as well as conferring the copolypeptide with fluorescence to allow for enhanced imaging. The fully peptidic nanostructures produced here demonstrate the potential for a biocompatible, biodegradable and pH-sensitive drug delivery system for use in anticancer therapy.

pH-sensitive histidine-based block copolypeptide nanostructures for drug delivery

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.