University of Maryland Baltimore Experimental Therapeutics Symposium 2009

1. Center of Cancer Nanotechnology Excellence University of Maryland Greenebaum Cancer Center Schools of Medicine & Pharmacy College Park Bioengineering

2. Cancer Nanotechnology – new field of research

3. Promise of nanotechnology in cancer therapy

4. NIH Cooperative Agreement Specialized Center (U54) CCNEs are designed to link physical scientists, engineers, and technologists working at the nanoscale with cancer biologists and oncologists specializing in the diagnosis, prevention, and treatment of cancer to enable multi-disciplinary team research. Network of CCNEs for the research and development of cancer-oriented techniques and tools based on nanotechnology, including the completion of the pre-clinical stage of development of nanotechnology-based solution to the clinically relevant cancer problem(s) Even though clinical trials are beyond the scope of this RFA, all CCNEs must be strongly committed to and capable of further translation of the technologies/tools under development

5. Other CCNE Aspects Need to demonstrate in depth expertise in clinical oncology, cancer biology & engineering aspects Cooperation with NCI Alliance for Nanotechnology in Cancer Current centers: UNC, Stanford, UCSD, Emory/Georgia Tech, MIT/Harvard, Northwestern, CalTech, WashU 5 years @ $16M (total cost) 8-10 Centers (likely ~60 applications) Pilot Projects, Training and Outreach, Inter-Alliance cooperation Core Facilities

6. Maryland Center for Cancer Nanotechnology Excellence Peter Swaan PI/PD Phil Deshong Co-PI/PD Alexander Edelman Mao Sausville Clinical Advisors Civin Cullen Shapiro Steering Committee Bentley Rubloff Moser Steering Committee Kofinas Training & Outreach Cytimmune SD Nanoscience Industrial Partners Pilot Projects Trans-Alliance Projects NIST NCI NCL External Partners Deshong Project 2 Nan Project 1 Fourkas Project 3 Shapiro Project 4 Paciotti Project 5 Lapidus Translational/Imaging Core Tan Bioinformatics & Data Sharing Core Swaan Analytical & PK/PD Core

7. Focus MD CCNE Focus: Pancreatic and Lung Cancer Thematic/programmatic areas of focus: Early diagnosis using in vitro assays and devices or in vivo imaging techniques. Multifunctional nano-therapeutics (theragnostics) and post-therapy monitoring tools. Unique Aspects: Materials Science, Fabrication, Manufacturing, GMP, PK/PD, demonstrated clinical trials experience with nanoconsructs

8. Core Projects Silicon Nanotubes for Image-guided targeted drug delivery (Nan, Lee) Targeted Delivery using Surfactant Nanovesicles (DeShong, English, Raghavan, Zachariah) Multiphoton Imaging of Functionalized Gold Nanorods (Fourkas) Delivery of Magnetic Particles (Ben Shapiro) Gold nanoparticle delivery & angiogenesis inhibitors (Paciotti)

9. Research Focus Pancreatic Drugs: Standard therapy: gemcitabine Cell Targets: Validated w/expertise: folate receptor Validated clinical: EGFR Unvalidated Novel: MUC1 Lung Drugs: Standard therapy: Cisplatin/Carboplatin, Novel/exploratory: Maytansine Cell Targets: Validated w/expertise: folate receptor Validated clinical: EGFR Unvalidated Novel: TTF1

11. passive diffusion into tissues, nondiscriminate

12. systemic toxicity limits dosing and efficacy

13. Macromolecular conjugation to therapeutics

14. limited to vesicular (endocytic) internalization

15. tumor tissue perfusion increased by EPR effect

16. Targeted macromolecular conjugates

19. essential for normal cellular metabolic functioning

24. FA-targeted polymers displayed this only in SKBR-3 cells.

25. The cellular accumulation of MMC was significantly higher following the endocytosis of nontargeted (P3A) and RF-targeted (P3B, P3C) polymer MMC conjugates.

28. Aim 2B: Anticancer efficacy of free and conjugated MMC in a breast cancer-induced nude ♀ mouse model.