Cancer

1. Cancer • Historically agents given systemically • Agents that kill rapidly dividing cells • Find therapeutic dose  Kills tumor cells w/o killing patient • Lots of side effects • Localized/targeted delivery is the holy grail • Nanomedicine!! • Also protection from degradation and increased solubility

3. Nanoparticles – drug throughout • Nanocapsules – drug w/in coating • PEGylation – makes stealthy • Ligand – binds to cell receptor for targeting

4. Tumor Vasculature • Irregularly shaped, big, and leaky • Lack of lymph drainage • High vessel density

5. Passive Targeting  EPR • Small drugs enter tumor and leave • Particles enter and stay • Long circulation time key

6. Active Targeting • EPR + something that binds tumor cells specifically

7. Targeting depends upon over-expression of surface molecules by tumor cells  Interfere with signaling when bind (targeting ligand and drug)  Ab tethered to drug  Ligand + drug

8. Paige

9. Paige Daruwalla, Cancer Science, 2010; 101; 1866-1874

10. Paige MoCR IC50=1.2 mM DLD-1 IC50=0.8 mM HT-29 IC50=0.85 mM MCF-7 IC50=0.8 mM Daruwalla, Cancer Science, 2010; 101; 1866-1874

11. Shrinidhi Daruwalla, Cancer Science, 2010; 101; 1866-1874

12. Shrinidhi Daruwalla, Cancer Science, 2010; 101; 1866-1874

13. Shrinidhi Daruwalla, Cancer Science, 2010; 101; 1866-1874

14. Anna Daruwalla, Cancer Science, 2010; 101; 1866-1874

15. Anna Daruwalla, Cancer Science, 2010; 101; 1866-1874

16. Anna Daruwalla, Cancer Science, 2010; 101; 1866-1874

17. Felix Daruwalla, Cancer Science, 2010; 101; 1866-1874

18. Kevin

19. Kevin Lehtinen, PLOS One, 2012; 7(7); e41410-

20. Inseong Lehtinen, PLOS One, 2012; 7(7); e41410-

21. Inseong Lehtinen, PLOS One, 2012; 7(7); e41410-

22. Maura background non-targeted pre-targeted direct target Lehtinen, PLOS One, 2012; 7(7); e41410-

23. Maura Lehtinen, PLOS One, 2012; 7(7); e41410

24. Michael Lehtinen, PLOS One, 2012; 7(7); e41410-