Iron-chelating PEG-like nanoprobes as therapeutic and 89Zr/PET imaging agents
Mentor: Georges El Fakhri, PhD (Massachusetts General Hospital)
Since iron is an essential element for cell growth and proliferation, iron chelation (removal) is a strategy for achieving cytostasis, inhibiting the division of cancer cells. The Josephson lab has developed PEG-like nanoprobes (PNs) that consist of the iron-chelator (iron binder) deferoxamine (DFO), a fluorochrome, and PEG polymer. These DFO bearing PNs (“DFO-PNs)” bind 89Zr (a radioactive metal ion detected by PET imaging) and can be imaged with PET/CT or by surface fluorescence (see Figure). Preliminary results indicate a DFO-PN can inhibit the growth of at least one tumor cell line. The goal of this project is to demonstrate that DFO-PNs can inhibit the division of a variety of tumor cell lines, using techniques for measuring the inhibition of cell division, instead of cell death, developed in the Josephson lab. Success of these experiments will support the use of DFO-PNs in animal models of cancer, and their possible clinical translation.
Imaging the tumor uptake of a DFO-PEG-like Nanoprobe (DFO-PN) by a mCherry expressing HT-29 tumor. Black and white CT images and color PET/CT images of two mice are shown at the (a) 1 h vascular phase, (b) 24 h vascular/tumor phase and, (c) 48 h tumor uptake phase. Red arrows show tumors. (d) Fluorescence images of two different mice from above are shown for the (d) pre-injection mCherry tumor fluorescence (purple), (e) 2 h vascular phase of DFO-PN fluorescence (green), (f) 24 h vascular and tumor phase of DFO-PN fluorescence and, (g) at the 48 h tumor phase. DFO-PN shows a slow uptake by the mCherry/HT-29 tumor by PET or fluorescence. Source: