Daniel A. Heller
Memorial Sloan-Kettering Cancer Center / Weill Cornell Medicine
We develop nanotechnologies to accelerate the research, diagnosis, and treatment of cancer and allied diseases. We focus on nanoparticle drug delivery systems and nanosensor-based diagnostics and drug discovery tools.
To build better cancer therapeutics, we investigate the potential to improve the therapeutic index of precision medicines via nanomedicine-based strategies to localize drugs to tumors using vascular targets. We developed machine learning processes to facilitate the encapsulation of diverse drug classes into these nanoparticles, based on drug molecular structure, resulting in the rapid synthesis of many, diverse, targeted nanotherapeutics. We found that P-selectin, expressed endogenously on activated endothelium in tumors, can be used as a nanotherapeutic target to improve the efficacy of kinase inhibitors and abrogate dose-limiting toxicities, to improve therapeutic in- dex. P-selectin can also be induced via ionizing radiation, enabling the enhancement of the target. We also found that endothelial targeting can improve delivery across intact blood-brain barriers for the treatment of intracranial tumors and metastases, via activating transendothelial transport. We also develop optical nanosensor technologies using carbon nanotubes to facilitate the longitudinal detection of cancer biomarkers and to build new assays for cancer drug development. These technologies employ the bandgap fluorescence of single-walled carbon nanotubes (SWCNTs) which emit in the near-infrared “tissue transparent” window and can respond to analytes down to the single-molecule level. We have developed new sensors for the detection of metabolic changes in live cells and tissues, disease biomarkers in situ via implants, and overall disease states, aided by machine learning processes.