• Like
  • Save
Swaan
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

Published

University of Maryland Baltimore …

University of Maryland Baltimore
Experimental Therapeutics Symposium 2009

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
284
On SlideShare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
0
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 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
  • 10. Vicent et al. J. Trends Biotechnol (2006)
    Chemotherapeutic Delivery
    • IV administration of low MW anticancer agents
    • 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
    • 17. exploits receptors which are upregulated in
    some cancer types
    • high-affinity ligands promote conjugate
    internalization through receptor-specific
    endocytosis
  • 18. Russell-Jones et al. J Inorg Biochem (2004)
    M. Phelps Dissertation, OSU (2005)
    Vitamins as Cancer-Specific Targeting Agents
    • B Vitamins
    • 19. essential for normal cellular metabolic functioning
    • 20. active internalization mechanisms (RME) enable efficient
    absorption of daily vitamin requirements (2.4 μg to 16 mg)
    • Vitamins and Cancer
    • 21. upregulated expression of cell-surface vitamin receptors to
    accommodate increased vitamin requirements
    • the extent of upregulation is highly variable between cancer types
    • 22. folic acid: FRα↑ in over 1/3 human cancers and > 90 %
    ovarian cancers
    • riboflavin (RF): absorption increased (~ 200 %) in breast
    cancer cells, as well as placental and ovarian
    M. Phelps Dissertation, OSU (2005)
  • 23. In-Vitro Characterization of RF-Targeting Potential in Human Breast Cancer Cells
    • RF-targeted polymer retains high affinity for internalization in both breast cancer cell lines (MCF-7, SKBR-3).
    • 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.
    • 26. Polymer-delivered MMC exhibited high cytotoxic potencies, most notably following RF-mediated delivery.
  • In-Vivo Analysis of RF-Targeted Polymer Conjugates
    AIM 1: Measure the biodistribution of nontargeted and RF-targeted polymer conjugates in a human breast cancer (MCF-7)-induced nude ♀ mouse model.
    • Aim 1A: Time-dependent distribution of polymer conjugates.
    • 27. Aim 1B: Effect of RF serum levels on polymer distribution.
    AIM 2: Measure the activity of free and nontargeted or RF-targeted polymeric MMC.
    • Aim 2A: Tolerability of free and conjugated MMC in healthy nude mice.
    • 28. Aim 2B: Anticancer efficacy of free and conjugated MMC in a breast cancer-induced nude ♀ mouse model.