(60a) Nanoparticle Cancer Therapeutics: Concept to Clinic

Nanoparticle-based therapeutics containing either small molecule anti-cancer agents (CRLX101 (formerly called IT-101); Phase II) or siRNA (CALAA-01; Phase I) are described. The key component in each nanoparticle is a cyclodextrin-containing polymer that endows it with multifunctional behavior. Relationships between nanoparticle design and function in animal models are illustrated. Results from preclinical animal models and human clinical trials are compared to illustrate similarities and differences between behaviors in animals and humans. For example, with CRLX101, features designed into the nanoparticles such as the ability to have long circulation times and long drug release in tumors cells has been observed in mice and humans. With CALAA-01, short circulation times observed in mice and non-human primates is also seen in humans. Additionally, the ability of CALAA-01 to release siRNA and have it perform RNAi inside of cancer cells within the tumors of animals and humans is verified using RACE analyses. While many of the features of the nanoparticles do translate from animals to humans, there are issues that do arise when treating humans. Some of these issues will be discussed.