Entry Date:
December 14, 2007

Nanoparticle-Based Cancer Biomarker Sensor

Principal Investigator Michael Cima

We are developing miniature medical implants for cancer detection and monitoring. The implant will contain wells filled with nanoparticles that can report on the conditions inside the tumor microenvironment, including concentrations of cancer biomarkers or chemotherapeutic drugs. This tool may be able to provide physicians and patients real-time information on the efficacy of treatment regimes.

Technologies for local monitoring of cancer biomarkers and chemotherapeutic drug concentrations will have far-reaching impact on cancer research and clinical care. The need is particularly important for monitoring the efficacy of treatments to bulky cancers with restricted delivery, or to cancers requiring optimized and personalized approaches. This project combines the sensing capabilities of nanoscale magnetic relaxation switches (MRS) and the versatility of microfabricated structures to create an implantable sensor that would be read by MRI. MRS are magnetic iron oxide nanoparticles that can be functionalized to detect a variety of analytes (Perez, Nature Biotech 2002). The presence of analyte causes the MRS to aggregate, causing a change in T2 (transverse spin-spin relaxation time). MRS are packaged into a device to contain and expose the MRS to the tumor milieu.

MRS were functionalized to detect the beta subunit of human chorionic gonadotrophin (hCG), which is elevated in testicular and ovarian cancers. The addition of hCG-ß to the MRS resulted in T2 shortening as seen in test-tubes and in prototype devices by NMR spectroscopy and MRI respectively. This biomarker sensor is being tested in cell lines producing hCG-ß and in nude mice bearing ectopic tumors. This is the first nanoparticle system to detect hCG-ß cancer biomarker via T2 shortening. This is also the first demonstration of T2 shortening response inside a semi-permeable implantable device. This method can be adapted to detect other circulating biomarkers.