1. Nanoparticles for Nanomedicine Neil S. Forbes Nanotechnology Institute University of Massachusetts, Amherst July 10, 2008 University of Massachusetts Chemical Engineering

2. Targeted Delivery to Tumors

3. Many Different Length Scales 10cm 1cm 100 m 1 m

4. Relative Size of Nanoparticles Nanoparticle with a 2 nm core and an octanethiol functionalized monolayer

5. Making Gold Nanoparticles AuCl4- salts are reduced using NaBH4 in the presence of thiol capping ligands The core size of the particles formed can be varied from <1 nm to ~ 8 nm The surface functionality can be controlled through the choice of thiols

6. Fluorophores and Drugs Selectively Dissociate Inside Cells

7. Control of Surface Charge

8. Investigating Delivery Using Cylindroids 100 m Plug Well Plate Microscope Objective Cylindroid Viable Dead

9. Nanoparticles in Cylindroids

10. Nanoparticle Diffusion 4hrs 24hrs d c a x y b D×10 7 cm 2 /sec

11. Modeling Particle Diffusion

12. How Does Particle Charge Affect Tissue Penetration? Transcellular Paracellular Cells A B

13. Engineering Approach: Targeted Intratumoral Therapy Quantify tumor microenvironments Develop vectors to target tumor quiescence Necrotic Quiescent Proliferating Therapeutic

14. Bacterial Penetration into Cylindroids 100 m

15. Microenvironments in Cylindroids Viability Acridine Orange Scale bar is 100 µ m Kasinskas, Forbes. 2006. Biotech Bioeng, 94:710

16. Bacteria Accumulate in Mouse Tumors

17. Control of Cytotoxicity 1.Inject modified bacteria 2.Induce peptide with radiation

18. Tumor Growth and Mouse Survival PBS Control Bacteria Cytotoxic Bacteria PBS + 2Gy Control Bacteria + 2Gy Cytotoxic Bacteria + 2Gy Cytotoxic Bacteria Control Bacteria PBS Bacteria + Radiation Control + 2Gy PBS + 2Gy Median survival doubles from 14.0 to 26.0 days

19. Effect of Double Dose Delayed growth 30.3 days 30-day survival increased from 0% to 100%

21. Cells A BC