Department of Cell Biology
263 Farmington Avenue
Farmington, CT 06030
- Use of heavy-atom nanoparticles for tumor imaging, vascular imaging and as a radiation enhancer for tumor therapy.
- Use of iron and gold nanoparticles for tumor hyperthermia
- Development of novel brain tumor therapies for experimental, advanced, imminently lethal intracerebral malignant gliomas and melanomas in rats and mice using a combination of radiation therapy and immunotherapy.
- Novel biomarkers in human breast cancer.
- Use of heavy atom nanoparticles to study vulnerable plaque in mouse models of atherosclerosis.
Our laboratory is involved in a number of research projects in the fields of cancer, cancer immunotherapy, cancer therapy, tumor and vascular imaging, as can be seen by the following publications. Please contact the Smilowitz Lab for specific projects.
1. Experimental Therapeutics of Brain Tumors: We introduce glioma or melanoma cells into rat or mouse brains and allow the tumors to occupy about 2% of the brain (analogous to human brain tumors at the time of diagnosis) before therapy is started. We first treat with a form of radiation therapy followed by a form of experimental immunotherapy under development. A variety of immunological assays are performed in addition to survival studies.
Henry M. Smilowitz, Peggy L. Micca, Daniel Sasso, Qian Wu, Nathanial Dyment, Lynn Kuo. (2016) Increasing radiation dose improves immunotherapy outcome and prolongation of tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma. Cancer Immunol Immunother 65:127–139.
Qiu Z, Huang H, Greiner J, Perez OA, Smilowitz HM, Adler B, Khanna KM. 2015. Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8(+) T-cell Response and Protects Mice from Melanoma. Cancer Immunology Research 3:0F1-0F11.
Smilowitz, H.M., Sasso, D., Lee, E., Goh, G., Micca, P.L., Dilmanian, F.A. 2013. Therapy model for advanced intracerebral B16 mouse melanoma using radiation therapy combined with immunotherapy. Cancer Immunology Immunotherapy 62:1187-1197.
Smilowitz, H.M., Slatkin, D.N., Micca, P.L., Miura, M. 2013. Microlocalization of lipophilic porphyrins, nontoxic enhancers of boron neutron capture therapy. International Journal of Radiation Biology 89:611-617.
Stoklasek, T., Colpitts, SL, Smilowitz, H.M. and Lefrancois, L 2010. MHC Class I and TCR avidity control the CD8 T cell response to IL15/IL15Ra complex. J. Immunol. 185: 6857-6865.
Smilowitz, H.M., Weissenberger, J.,O’Neill, R.,Brown, J., Weis , J. and Laissue, J.A. 2007. Orthotopic transplantation of v-src expressing glioma cell lines into immunocompetent mice: establishment of a new transplantable in vivo model for malignant gliomas. J. Neurosurgery 106: 1-8 (PMID 18644191).
Smilowitz, H.M., D.N. Slatkin, N. Lubimova, H. Blattman, E. Brauer-Krisch, A. Bravin,M. Di Michiel, J. Stepanek, G. Le Duc, J.-O. Gebbers, J.A. Laissue. 2006. Synergy of gene mediated immunoprophylaxis and microbeam radiation therapy (MRT) for advanced intracerebral rat 9L gliosarcomas. J. Neuro-Oncology 78:135-143 (PMID 16598429).
Smilowitz, H.M., J.A. Coderre, M.M. Nawrocky, A. Pinkerton, W. Tu and D.N. Slatkin. 2002. The combination of X-ray-mediated radiosurgery and gene-mediated immunoprophylaxis of an advanced intracerebral gliosarcoma in rats. J. Neuro-Oncology. 57: 9-18 (PMID12125969).
Laissue, J.A., H. Blattmann, M. Di Michiel, D.N. Slatkin, N. Lyubimova, R. Guzman, W. Zimmermann, T. Bley, P. Kircher, R. Stettler, R. Fatzer, A. Jaggy, H.M. Smilowitz, E. Brauer, A. Bravin, G. Le Duc, C. Nemoz, M. Renier, W. Thomlinson,J. Stepanek and H.P. Wagner.2001. Weanling piglet cerebellum: a surrogate for tolerance to MRT (Microbeam Radiation Therapy) in pediatric neuro-oncology. In. Penetrating Radiation Systems and Applications III, H. Roehrig, F. P. Doty, R. C. Schirato, E.J. Morton, Editors. Proceedings of SPIE, 4508: 65-73 (PMID N/A).
Miura, M., D.D. Joel, H.M. Smilowitz, M.M. Nawrocky, P.L. Micca, D.A. Hoch, J.A. Coderre and D.N. Slatkin. 2001. Biodistribution of copper carboranyltetraphenylporphyrins in rodents bearing human or isogeneic neoplasms. J. Neuro-Oncology, 52: 111-117 (PMID11508810).
Weiner, R.E., D.E. Sasso, M.A. Gionfriddo, R.S. Thrall, S.S. Syrbu, H.M. Smilowitz, and J.Vento. 2001. Early detection of oleic acid-induced acute lung injury in rats using 111In-labeled antibody directed against intracellular adhesion molecule-1. J. Nuclear Medicine, 42: 1109-1115 (PMID 11438635).
Smilowitz, H.M., D.D. Joel, D.N. Slatkin, P.L. Micca, M.M. Nawrocky, K. Youngs, W. Tu and J.A. Coderre. 2000. Long-term immunological memory in the resistance of rats to transplantable intracerebral 9L gliosarcoma (9LGS) following subcutaneous immunization with unmodified and X-irradiated 9LGS. J. Neuro-Oncology, 43:193-203 (PMID 10902851).
Smilowitz, H.M., P.L. Micca, M.M. Nawrocky, D.N. Slatkin, W. Tu and J.A. Coderre. 2000. The combination of boron neutron-capture therapy and immunoprophylaxis for advanced intracerebral gliosarcomas in rats. J. Neuro-Oncology, 43:231-240 (109032854).
2. Gold and Iodine Nanoparticle Enhanced Radiation Therapy; Vascular and Tumor Imaging; Gold and Iron Nanoparticle Hyperthermia. We are working collaboratively with a company on Long Island that has developed novel preparations of heavy-atom nanoparticles. These non-toxic particles can be injected iv at very high doses. Larger particles circulate for extended periods, while smaller particles are excreted by the kidney. We are working on several projects to develop novel therapies and diagnostic tests that can be performed with these agents:
· Gold and Iodine Nanoparticle Enhanced Radiation Therapy: We have shown that gold nanoparticles can greatly increase the radiation dose a tumor receives and are therefore useful as radiation enhancers. We are currently working on breast cancer, bladder cancer, squamous cell carcinoma and glioma models using gold and other heavy-atom nanoparticles.
· Gold and Iodine Nanoparticle Enhanced Imaging: We are working on several imaging projects including the development of virtual colonoscopy, breast cancer imaging, gold-based angiography, and kidney imaging.
· Iron and Gold Nanoparticle Mediated Hyperthermia: We are developing novel therapies whereby gold and iron nanoparticles can be used to treat tumors with hyperthermia.
Ridwan SM Hainfeld JF, Ross V, StanishevskiyY, Smilowitz HM. 2020. Novel Iodine Nanoparticles Target Vascular Mimicry in Intracerebral Triple Negative Human MDA-MB-231 Breast Tumors. Scientific Reports. Accepted. Being Published Jan 13, 2021.
Hainfeld JF, Ridwan SM, Stanishevskiy FY, Smilowitz HM. 2020. Iodine Nanoparticle Radiotherapy of Human Breast Cancer Growing in the Brains of Athymic Mice. Scientific Reports. 2020 Sep 24;10(1):15627. doi: 10.1038/s41598-020-72268-0.PMID: 32973267
Ridwan SM, El-Tayyeb F, Hainfeld JF, Smilowitz HM. 2020. Distributions of IV Injected Iodine Nanoparticles in Orthotopic U87 Human Glioma Xenografts Over Time and Tumor Therapy. Nanomedicine. doi: 10.2217/nnm-2020-0178. Online ahead of print.PMID: 32975163
Hainfeld JF, Ridwan SM, Stanishevskiy Y, Smilowitz HM. 2020. Iodine Nanoparticles In Dr Jan Schuemann J, Bagley A, Berbeco R, Bromma K, Butterworth KT, Byrne H, Chithrani DB, Professor Cho SH, Cook J, Favaudon V, Gholami YH, Gargioni E, Hainfeld JF, Hespeels, F, Heuskin A-C, Ibeh UM, Kuncic Z, Kunjachan, S, Lacombe S, Lucas S, Lux F, McMahon SJ, Nevozhay D, Ngwa W, Payne JD, Penninckx S, Porcel E, Prise KM, Rabus H, Ridwan SM, Rudek B, Sanche L, Singh B, Smilowitz HM,Sokolov KV, Sridhar S, Stanishevskiy Y, Sung W,Tillement O, Virani NA, Yantasee W, Krishnan S. 2020. Roadmap for metal nanoparticles in radiation therapy: current status, translational challenges, and future directions. Physics in Medicine & Biology doi: 10.1088/1361-6560/ab9159.
Hainfeld JF, Ridwan SM, Stanishevskiy Y, Panchal R, Slatkin DN, Smilowitz HM. 2019. Iodine nanoparticles enhance radiotherapy of intracerebral human glioma in mice and increase efficacy of chemotherapy. Sci Rep. 2019 Mar 14;9(1):4505. doi: 10.1038/s41598-019-41174-5.
James F. Hainfeld, Sharif M. Ridwan, Yaroslav Stanishevskiy,Nathaniel R. Smilowitz, James Davis, Henry M. Smilowitz. Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging. Sci Rep. 2018 Sep 14;8(1):13803.
Smilowitz HM, Tarmu LJ, Sanders MM, Taylor JA 3rd, Choudhary D, Xue C, Dyment NA, Sasso D, Deng X, Hainfeld JF. Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice. 2017 Oct 27;12:7937-7946. doi: 10.2147/IJN.S140977. eCollection 2017.
Sung W, Ye SJ, McNamara AL, McMahon SJ, Hainfeld J, Shin J, Smilowitz HM, Paganetti H, Schuemann J. Correction: Dependence of gold nanoparticle radiosensitization on cell geometry. Nanoscale. 2017 Aug 10;9(31):11338. doi: 10.1039/c7nr90158e.
Sung, Wonmo; Ye, Sung-Joon; McNamara, Aimee L; McMahon, Stephen J; Hainfeld, James; Shin, Jungwook; Smilowitz, Henry M; Paganetti, Harald; Schuemann, Dependence of gold nanoparticle radiosensitization on cell geometry. Nanoscale, 2017, 9, 5843-5853.
Hainfeld, J.F., Lin L, Slatkin D.N., Dilmanian F.A., Smilowitz H.M. 2014. Gold nanoparticle hyperthermia reduces radiatiotherapy dose. Nanomedicine: Nanotechnology, Biology and Medicine. 10:1609-1617.
Hainfeld, J.F., O’Connor, M.J., Lin, P., Qian, L., Slatkin, D.N. Smilowitz, H.M. 2014. Infrared-transparent gold nanoparticles converted by tumors to infrared absorbers cure tumors in mice by photothermal therapy. PLoS 9:e88414.
Hainfeld, J.F., Smilowitz, H.M., O’Connor, M.J., Dilmanian, F.A., Slatkin, D.N. 2012. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine London (Future Medicine).8:1601-1609.
Hainfeld, J.F., O’Connor, M.J., Dilmanian, F.A., Slatkin, D.N., Adams, D.J., Smilowitz, H.M. 2011. MicroCT enables microlocalization and quantification of Her-2-targeted gold nanoparticles within tumor regions. British Journal of Radiology, 84:526-533.(PMID 21081567).
Hainfeld, J.F., O’Connor, M.J., Lin, P.P., Smilowitz, H.M. 2010 Cancer therapy with wIRA and gold nanoparticles in water-filtered and infrared-A radiation: From Basic Principles to Clinical Applications.
Hainfeld, J.F., Dilmanian, F.A., Zhong Z., Slatkin, D.N., Smilowitz, H.M. 2010. Gold nanoparticles enhance radiation therapy of a squamous cell carcinoma growing in mice. Physics in Medicine and Biology, 55: 3045-3059 (PMID 20463371).
Hainfeld, J.F., Slatkin, D.N., Dilmanian, F.A., Smilowitz, H.M. 2008. Radiotherapy enhancement with gold nanoparticles. J. Pharmacy and Pharmacology, 60: 977-985 (PMID 18644191) Volume 60 #8. is a Special Issue: Radiation Biology – Can New Concepts Achieve Better Treatment Outcomes? JPP has informed us that this paper is one of the top 25 most downloaded papers in 2008, >100X through 12/08.
Hainfeld, J.F., Slatkin, D.N., Focella, T., Smilowitz, H. 2006. Gold nanoparticles as X Ray contrast agents. British Journal of Immunology. 79: 248-253 (PMID 16498039).
Hainfeld, J.F., Slatkin, D. N., Smilowitz, H.M. 2004. The use of gold nanoparticles to enhance radiotherapy in mice. Physics in Medicine and Biology, 49: N309 (PMID 15509078). Note: This paper has been selected for inclusion in Institute of Physics (IOP) Select, Institute of Physics, London, England.
3. Novel Biomarkers in human breast cancer. Blood samples from women with breast cancer are being screened for the presence of novel biomarkers that may be linked to more aggressive disease.