Abstract: The present invention provides drug delivery systems comprising FcRn binding partners (e.g., FcRn binding partner, Fc fragment) associated with a particle or an agent to be delivered. Inventive drug delivery systems allow for binding to the FcRn receptor and transcytosis into and/or through a cell or cell layer. Inventive systems are useful for delivering therapeutic agents across the endothelium of blood vessels or the epithelium of an organ.

Abstract: Screening of a library of particles in vivo and/or in vitro using Polyplex Iterative Combinatorial Optimization (PICO) allows for the design of particles for targeting a specific organ, tissue (e.g., cancer), or cell. Particles may, for example, include different targeting agents (e.g., aptamers or plurality of aptamers) on their surfaces, and the aptamer or aptamers may be evolved to provide better targeting of the particles. Libraries of particles are enriched in characteristics of particles that have been found to migrate to a tissue of interest, be taken up by cells, etc. The process may be repeated to engineer particles of a desired specificity or biological function.