(31a) Biomaterial-Cell Interface: Implications for Drug Delivery

Polymeric nanoparticles have found application in varied fields including drug delivery and medical imaging. The behavior of therapeutic nanoparticles in the body is determined by their interactions with cells including macrophages, endothelial cells and cancer cells. Such interactions determine their therapeutic performance including circulation half-life, drug release rates and toxicity. My talk will focus on recent advances in engineering of nanoparticles to control their biological interactions. In particular, I will focus on how physical attributes of particles including shape and deformability can be controlled to improve fundamental understanding of cell-material interactions and therapeutic performance of carriers. We have devised methods to generate particles of several distinct morphologies and studied their impact on key processes in drug delivery including phagocytosis, circulation, adhesion of vascular walls, and targeting. Based on this understanding, we have designed novel particles that demonstrate enhanced targeting.

Our studies demonstrate that particle morphology provides a new dimension in engineering of polymeric carriers and opens up new opportunities in drug delivery. In addition to morphology, we also demonstrate that controlling mechanical properties of carriers also offers unique opportunities. Specifically, we have synthesized flexible particles made from proteins that mimic the physical and functional properties of body’s own circulating cells such as red blood cells and platelets. Particles that mimic the size, shape and flexibility of natural circulating cells offer advantages that are typically lacking in conventional spherical polymeric particles.

The motivation to use physical properties of nanoparticles to control biological function is provided by the biology itself. In nature, numerous examples can be found where physical aspects, such as shape, mechanical properties and compartmentalization are crucial to biological function. Physical attributes such as size, shape and mechanical properties form essential building blocks of biology. This realization forms the basis of the new paradigm in design of nanoparticles.