Targeting Drugs to the Tumor Microenvironment: We are developing nanomedicines to target precision agents to disease sites, including to cancer metastases. Many cancer drugs, even newer personalized medicines, cause side effects that limit their effectiveness. We built nanoparticle platforms to target many different classes of drugs to blood vessels that feed tumors. One of our new technologies targets nanoparticle drug carriers to P-selectin, a protein on tumor vessels that can be induced by low doses of radiotherapy, allowing us to target nearly any type of tumor. A second type of nanoparticle targets caveolae on tumor blood vessels. We found that these nanoparticles can direct drugs to tumors more effectively to reduce side effects and enhance anti-tumor effects.
Nanoinformatics: We are developing machine learning algorithms to enable the assembly of nanomedicines loaded with many types of precision drugs.
Kidney-Targeted Therapeutics: We are synthesizing nanoparticles that specifically target the kidneys. These will facilitate the development of new medicines to address many types of kidney diseases.
Drug delivery to brain cancers: We are studying mechanisms involved in nanoparticle transport across the blood-brain barrier and developing strategies to improve drug delivery to brain cancers and neurologic diseases.
Nano-Size Particles Carry Personalized Medicines to Cancer’s Doorstep
D Tylawsky, H Kiguchi, J Vaynshteyn, J Gerwin, J Shah, T Islam, M Snuderl, M Greenblatt, D Boué, Y Shamay, P Raju*, DA Heller* “P-selectin-targeted nanocarriers induce active crossing of the blood-brain barrier via caveolin-1-dependent transcytosis.” Nature Materials 22 (2023) 391-399.
NB Tannan, MT Manzari, LM Herviou, M Da Silva Ferreira, C Hagen, H Kiguchi, Z Asgari, K Manova-Todorova, V Seshan, E de Stanchina, DA Heller, A Younes*. “Dual Inhibition of MCL1 and BCL2 in Lymphoma Using Tumor Targeted Nanoparticles for Drug Delivery” Blood (2020) blood.2020008017. https://pubmed.ncbi.nlm.nih.gov/33067607/
Y Shamay, J Shah, DF Tschaharganeh, D Roxbury, J Budhathoki-Uprety, M Işık, A Mizrachi, K Nawaly, JL Sugarman, E Baut, MR Neiman, DC Johnson, R Sridharan, KL Chu, VK Rajasekhar, JD Chodera, SW Lowe, DA Heller*, “Quantitative Self-Assembly Prediction Yields Targeted Nanomedicines” Nature Materials (2018)
A Mizrachi, Y Shamay, J Shah, S Brook, J Soong, V Rajasekhar, J Humm, J Healey, S Powell, J Baselga, DA Heller*, A Haimovitz-Friedman*, M Scaltriti*: “Tumor-specific PI3K inhibition via nanoparticle delivery in head and neck squamous cell carcinoma.” Nature Communications 8 (2017) 14292.
Yosef Shamay, Moshe Elkabets, Hongyan Li, Janki Shah, Samuel Brook, Feng Weng, Keren Adler, Emily Baut, Maurizio Scaltriti, Prakrit V. Jena, Eric E. Gardner, John T. Poirier, Charles M. Rudin, Jose Baselga, Adriana Haimovitz-Friedman, Daniel A. Heller: ”P-selectin is a nanotherapeutic delivery target in the tumor microenvironment.” June 29, 2016 8 345ra87