1. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology A Promising Chemotherapy Agent, Gd@C82(OH)22 Ning Zhang Tianjin Medical University Cancer Institute and Hospital UICC 2008

2. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Chemotherapies have always been accompanied with serious side effects. Can nanoparticles provide a new approach to design low toxic therapeutic agents?

3. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Treatments with Gd@C 82 (OH) 22 Inhibit hepatoma growth in a mouse model Nano Lett Vol 5, pg 2050 Gd@C 82 (OH) 22 inhibits tumor growth in a breast tumor model. 0.28 mg/kg 1.20mg/kg

4. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Gd@C 82 (OH) 22 doesn’t show cytotoxicity

5. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Treatments with Gd@C 82 (OH) 22 reduced blood supply to tumors

6. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Treatments with Gd@C 82 (OH) 22 reduced blood vessel density

7. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Treatments with Gd@C 82 (OH) 22 induced a massive leukocyte infiltration in tumors.

8. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Gd@C 82 (OH) 22 induced iDC maturation and TH-1 response.

9. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Treatments Metastasis Rate Saline q.d. ×20 day 66.7% C 60 (C(COOH) 2 ) 2 (0.4 mg/kg, n = 10) 34.2% C 60 (OH) 20 (0.4 mg/kg, n = 10) 38.0% Gd@C 82 (OH) 22 ， 0.35mg/kg q.d. ×20 day 4.3 % Treatments with Gd@C 82 (OH) 22 cancer cell chemotaxis and metastasis

10. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Summary 1.Treatment with Gd@C82(OH)22 inhibits tumor growth without detectable toxicity. 2. Gd@C 82 (OH) 22 doesn’t show cytotoxicity. 3. Gd@C 82 (OH) 22 inhibits blood supply to tumor tissues. 4. Gd@C 82 (OH) 22 induced tumor immunity. 5. Gd@C 82 (OH) 22 inhibits cancer cell chemotaxis Blood supply Tumor immunity Metastasis

11. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Chinese Academy Institute of High Energy Physics Tianjin Cancer Institute and Hospital Research Center for Cancer Nanotechnology National Center of Nanotechnology

12. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Acknowledgements Nanosafety Lab, Chinese Academy of Science Dr. Yuliang Zhao, Director Dr. Gengmei Xing Huan Meng Laboratory of Molecular Immunoregulation, NCI Dr. Joost Oppenheim, Chief Dr. De Yang Dr. Yujie Ma Dr. Guoguang Ying Dr. Ruifang Niu

13. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Gd@C82(OH)22 induced a dendritic cell maturation

14. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology HR (100 ug/ml)-treated DCs migrated to SLC but not Rantes, suggesting the HR-treated DCs were mature DCs. Gd@C82(OH)22 induced a dendritic cell to express CCR7 receptors

15. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology T cell cytokine production in response to Gd@C82(OH)22 -treated DCs

16. Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Tianjin Medical University Cancer Institute & Hospital Research Center for Cancer Nanotechnology Treatments with Gd@C82(OH)22 disrupted the integrity of capillary blood vessels in tumors.