Magnetic Resonance Imaging-Guided Drug Delivery to Breast Cancer Stem-Like Cells

The feasibility of detecting breast cancer stem-like cells (BCSCs) with magnetic resonance imaging using extradomain-B of fibronectin (EDB-FN)-specific peptide (APT(EDB))-conjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (APT(EDB)-TCL-SPIONs) is previously demonstrated. Here, doxorubicin (Dox)-loaded APT(EDB)-TCL-SPIONs (Dox@APT(EDB)-TCL-SPIONs) are generated and their theranostic ability in a BCSC xenograft mouse model is assessed. The Dox@APT(EDB)-TCL-SPIONs enable more efficient delivery of Dox to tumors than nontargeted Dox@TCL-SPIONs. Much greater inhibition of BCSC tumor growth is observed after treatment with the Dox@APT(EDB)-TCL-SPIONs than with either Dox@TCL-SPIONs or free Dox. Hypointense signals are observed in the majority of the mice in postcontrast but not precontrast T2*-weighted MR images of tumors 7 days after treatment with Dox@APT(EDB)-TCL-SPIONs. An inverse correlation is observed between signal intensity and both EDB-FN expression and response to chemotherapy. The data indicate Dox@APT(EDB)-TCL-SPIONs can detect BCSCs within tumors by targeting EDB-FN-expressing cells. These nanoparticles thus have theranostic potential in breast cancer.