It has been shown that the morphology of nanomaterials greatly impacts the pharmacokinetic profile of the material, with larger objects having longer circulation times while smaller nanomaterials show a greater rate of internalization into cells. We have developed two nanoparticle systems (DNA- and peptide-polymer micellar systems) that combine these properties and allow us to program pharmacokinetics in vivo by virtue of morphology switches via endogenous or exogenous stimuli. We show, the circulation half-life of DNA containing polymeric micelles in blood in vivo can be modulated via a programmed morphology switch triggered by an exogenously injected DNA stimulus.  The second system utilizes peptide polymer amphiphiles that is responsive to specific cancer-associated enzymes. We have shown that these materials undergo a morphology switch from small sphere to large aggregate in tumor tissue in vivo resulting in the accumulation of the materials in the diseased tissue. These two systems have broad implications for the design of nanoscale materials in drug delivery and diagnostics applications where tunable pharmacokinetics can play a role in enhanced targeting and clearance.

Assembling, disassembling, and switching nanoparticles in vivo to program the phamacokinetics of therapeutic and diagnostic delivery vehicles

245th National Meeting (2013)

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