(51b) Delivering Nanoparticles to Lungs and Brain Via Hitchhiking On Red Blood Cells

Nanoparticulate drug delivery systems are one of the most widely investigated approaches for development of novel therapeutic strategies for a variety of diseases. However, rapid clearance by the reticuloendothelial system (RES) and lack of targeting to sites of interest prevent the clinical translation of nanoparticle therapies. Here, the unique flexibility, circulation times and vascular mobility of red blood cells (RBCs) are utilized to circumvent these roadblocks (Cellular Hitchhiking). 200nm nanoparticles non-covalently anchored onto RBC surface have been shown to increase circulation time and significantly reduce clearance by RES [1, 2].  In this work, Cellular Hitchhiking is used to reduce nanoparticle accumulation in RES organs (liver and spleen) and increase accumulation in all other organs, notably lungs and brain. RBC-hitchhiked nanoparticles exhibited ~7-fold higher accumulation in lungs and over 20-fold higher accumulation in the brain. Surprisingly, this accumulation was higher than that achieved by coating the nanoparticles by commonly used targeting antibodies for both lungs and brain. Further, we show that hitchhiking and antibody-mediated targeting approaches can be combined to further enhance tissue accumulation past that of either hitchhiking or antibody targeting alone. Parameters defining mechanisms for enhanced lung and brain accumulation, and its therapeutic potential will be discussed. These results highlight the efficacy of Cellular Hitchhiking in providing a new platform for targeted delivery of therapeutic agents for treatment of various cardiopulmonary, respiratory and neurodegenerative diseases.

1.  Chambers, E. and S. Mitragotri, Long circulating nanoparticles via adhesion on red blood cells: mechanism and extended circulation. Exp Biol Med (Maywood), 2007. 232(7): p. 958-66.

2.  Chambers, E. and S. Mitragotri, Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J Control Release, 2004. 100(1): p. 111-9.