California Institute of Technology,
Summary:We have translated nanoparticles (CRLX-101 and CALAA-01) into the clinic for treating patients with solid cancers. One of these nanoparticle, experimental therapeutics was the first to show functional RNA interference (RNAi) in humans. Lessons learned from these translational and clinical experiences are discussed. Currently, we are concentrating on developing nanoparticles that cross the blood-brain barrier (BBB). We have demonstrated that brain uptake of targeted nanoparticles can be increased by adding a linkage between transferrin (Tf) that is used to target the transferrin receptor on the BBB and the nanoparticle core that is cleavable during the transcytosis process. Results from several preclinical rodent models of brain cancer are presented and reveal that the targeted nanoparticles with cleavable linkages are able to produce efficacy even in models with intact BBBs. Implications for translating this type of nanoparticle into human clinical studies are discussed.