TUNABLE LEUKOCYTE-BASED BIOMIMETIC NANOPARTICLES AND METHODS OF USE

Disclosed are liposomal formulations and biomimetic proteolipid nanoparticles that possess remarkable properties for targeting compounds of interest to particular mammalian cell and tissue types. Leukocyte-based biomimetic nanoparticles are disclosed that incorporate cell membrane proteins to transfer the natural tropism of leukocytes to the final delivery platform. However, tuning the protein integration can affect the in vivo behavior of these nanoparticles and alter their efficacy. Here it is shown that, while increasing the protein:lipid ratio to a maximum of 1:20 (w/w) maintained the nanoparticle's structural properties, increasing protein content resulted in improved targeting of inflamed endothelium in two different animal models. The combined use of a microfluidic, bottom-up approach and tuning of key synthesis parameter enabled the synthesis of reproducible, enhanced biomimetic nanoparticles that have the potential to improve treatment of inflammatory-based conditions through targeted nanodelivery, including particular cancers such as human breast cancer, and TNBC in particular.