Multivalent Targeted Theranostic Liposomes for Chemoresistant Aggressive CaP

According to the National Cancer Institute, an estimated 233,000 men will be diagnosed with prostate cancer (CaP) in 2014, forever impacting their lives and their families' lives. Diagnosis and treatment of this disease has improved in recent years as scientists and clinicians better understand the role and function of the biological pathways and progression of the disease. However, significant effort is still needed to develop new methodologies to better identify, assess disease progression, and treat CaP with fewer detrimental side effects on the affected individuals. This proposal addresses the Fiscal Year 2014 Prostate Cancer Research Program overarching challenges of (1) developing better tools for early detection of disease and (2) developing effective treatments and addressing mechanisms of resistance in aggressive CaP. Specifically, the proposal addresses the focus areas of imaging, mechanisms of resistance, and therapy. The objective of the proposed research is to develop new theranostic (Thx) liposomes -- tiny particles that combine components for detection and treatment into a single package -- and perform preliminary tests to ensure these agents will identify and kill CaP cells. These Thx agents are designed to bind to a broad spectrum of CaP cells by interacting with three protein receptors observed on the outside surface of CaP cells that are not present on regular cells in the body. This strategy will allow delivery of Thx agents to CaP cells at early and late stages of the disease. In particular, this approach is specifically designed to enhance treatment of CaP cells that are resistant to standard therapy and that are associated with recurrence of the disease. These targeted Thx molecules are envisioned to help doctors specifically find the location of CaP cells in the body using non-invasive imaging procedures with current medical instrumentation and provide doctors with a stain for surgical selection of tumor margins. CaP patients at all stages of the disease would benefit from the improved imaging sensitivity of these Thx liposomes. Individuals in transition from primary to advanced stages, especially when the disease first starts spreading throughout the body, would be most benefited by the proposed work. Patients that are at risk to recurrent, non-responsive, and drug-resistant disease would gain tremendous benefit from the synergic therapeutic aspects of the proposal. Overall, this fundamental investigation using multiple targeted Thx liposomes would improve the patients' prognosis by enhancing disease assessment and control with decreased therapeutic toxicity to non-target tissues compared to systemically administrated therapies.