Dr. Marie-Christine Daniel discusses the development of multifunctional gold nanoparticle-based nanovectors for targeted cancer therapy. The nanovectors aim to overcome challenges in chemotherapy by preferentially delivering therapeutic drug combinations and imaging agents to tumor sites. Three projects focus on pancreatic, breast, and prostate cancers. The nanovectors incorporate dendrons for multifunctionalization, with targeting moieties, drug conjugates, and MRI contrast agents. Preliminary in vitro testing evaluates targeting efficacy and cytotoxicity against relevant cancer cell lines.

1. Dr. Marie-Christine Daniel, Chemistry & Biochemistry Department University of Maryland Baltimore County Multifunctional Nanovectors for Cancer Therapy: New Drug Delivery Systems for Pancreatic, Breast and Prostate Cancer Therapies

2. Ideal drug Main Challenge in Chemotherapy: Targeting

5. What are NANOvectors ?

6. Dendronized gold nanoparticles Au + D I Targeting Chemotherapeutic Drug D Imaging Au E D D T E I T T I Chemotherapeutic Drug E STRATEGY OF THE PROJECTS

7. DENDRIMER DENDRON Au GOLD NANOPARTICLE Ligands Generation numbers Core Termini Focal point Comparison Gold nanoparticle/ dendrimer/ dendron

10. Common starting dendron

11. Spacer and backbone dendron formation Backbone dendron Spacer :

12. Imaging dendron Gd(DOTA) - Gd 3+

14. Pancreatic Cancer: Targeting dendron Transferrin

15. Pancreatic Cancer: Gemcitabine-dendron Gemcitabine: Linkage through imine bond: pH-sensitive Stable in physiological plasma pH (7.4) But cleaved inside lysosomes (pH 4.5) Imine bond

16. Pancreatic Cancer: Anti-RON-dendron HS-CH 2 -CH 2 -NH 2 Pepsin Anti-RON

17. Pancreatic Cancer: Nanovectors Au + T T D I Transferrin Gemcitabine Anti-RON antibody I D T D T I D I D T D T I D I D T T D T T I D T D D I I D T T D I

19. Metastatic Breast Cancer: Docetaxel-dendron Docetaxel Docetaxel analog

20. Metastatic Breast Cancer: Epirubicin-dendron Epirubicin:

21. Metastatic Breast Cancer: Nanovectors Au + D I Transferrin Docetaxel MRI contrast agent Au E D D T E I T T I Epirubicin

23. Hormone-Refractory Prostate Cancer: targeting dendron HS-CH 2 -CH 2 -NH 2 Pepsin Anti-CD166 Coupling with maleimide

24. Hormone-Refractory Prostate Cancer: Prednisone-dendron Acyl hydrazone

25. Hormone-Refractory Prostate Cancer: Nanovectors Au + D I Anti-CD166 Docetaxel MRI contrast agent Au P D D T P I T T I Prednisone