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.
News
MSK News: Improving nanoparticle drug-loading efficiency
MSK News: Using nanoparticles to deliver complex cancer drugs safely by targeting tumor blood vessels
MSK News: Getting Drugs Across the Blood-Brain Barrier Using Nanoparticles
Nature Materials News & Views
Nano-Size Particles Carry Personalized Medicines to Cancer’s Doorstep
Hacking Metastasis: Nanotechnology Researchers Find New Way to Target Tumors
Nanoparticles Help Drugs Target Head and Neck Cancers with Reduced Side Effects
Miniature Device Could Unlock the Promise of Some Kidney Cancer Drugs
Publications
Vogt KC, Panagiotakopoulou M, Manzari Honu MT, Perea AM, Hu X, Yu X, Raziuddin R, LaPlant Q, Ruiz S, Raju GP, Jin J, Scheinberg DA, Heller DA*. Tumor microenvironment-targeted PROTAC nanoparticle self-assembly broadly predicted by structural descriptors. Sci Adv. 2025 Dec 5;11(49):eadu2292.
Highlighted in: MSK news
N Berisha, A Farahpour, M Ramakrishnan, C Chen, SA McPhee, T Wang, T-D Li, K Hema, M Panagiotakopoulou, V Athiyarath, M Coste, Y Marciano, E Sherman, RV Ulijn*, DA Heller*. “Directed discovery of high-loading nanoaggregates enabled by drug-matched oligo-peptide excipients.” Chem (2025) 102404.
Highlighted in: MSK news, Chemical & Engineering News, and Chem.
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.
Manzari, M.T., Shamay, Y., Kiguchi, H. et al. Targeted drug delivery strategies for precision medicines. Nat Rev Mater 6, 351–370 (2021). https://doi.org/10.1038/s41578-020-00269-6
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)
RM Williams, J Shah, HS Tian, Xi Chen, F Geissman, EA Jaimes, DA Heller*, “Selective Nanoparticle Targeting of the Renal Tubules.” Hypertension (2017) In press.
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
RM Williams, J Shah, BD Ng, DR Minton, LJ Gudas, C Park, DA. Heller*: “Mesoscale Nanoparticles Selectively Target the Renal Proximal Tubule Epithelium.” Nano Letters 15 (2015) 2358-2364.
