The conjugation of biological molecules such as proteins to synthetic polymers creates a promising new class of materials, where the protein is able to impart several characteristics lacking in traditional polymeric nanocarriers. While polymers are tunable and versatile in their production, proteins are capable of biological responses, enzymatic activity and structural control that polymers do not inherently possess. This new class of materials provides us with potential for overcoming certain challenges associated with therapeutic delivery such as targeting and biocompatibility.<br/><br/>Our group recently developed a self-assembled pH-responsive poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) nanoparticle system that assembles into nanoparticles of ~150 nm in diameter at pH 8 and disassembles when the pH is lowered below 6.8 at physiological temperature (37 °C). Here, we present new extension to this work in which we have successfully conjugated the pH-responsive polymers poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) and poly(2-(diethylamino)ethyl methacrylate)-ran-poly(2-(diisoproprylamino)ethyl methacrylate) (PDEAEMA-r-PDPAEMA) to a model protein, holo-transferrin. We characterized their assembly into uniform micelles of ~70 to 80 nm in diameter, studied their pH-dependent disassembly and cellular behaviour. Notable for the system is the translation of the pH-responsive nature of polymers to the conjugate, in which the pH of disassembly of the micelles was tuned depending on the polymer constituent attached to holo-transferrin.

Self-assembled transferrin-polymer conjugate nanocarriers for the delivery of therapeutics

253rd National Meeting (2017)

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