Radiolabeled block copolymer micelles for image-guided drug delivery

© 2016 Elsevier B.V. All rights reserved
We aimed at exploring block copolymer micelles (BCMs) for the simultaneous delivery of radiation/chemotherapy to cancer cells. To achieve that goal, we have prepared and characterized a novel type of docetaxel (DTX) loaded and non-loaded BCMs. The micelles were decorated with pyrazolyl-diamine chelating units to stabilize the matched pair 99mTc/Re for image-guided delivery of therapeutic drugs. The in vitro studies have shown that DTX release is pH-dependent increasing at lower pH values. Anti-proliferative studies in different cancer cell lines showed that DTX-loaded BCMs present relevant anti-proliferative activity. In comparison to free DTX, the loaded-micelles exhibited higher anti-proliferative activity for the same DTX concentration, which mean that a similar therapeutic outcome may be achieved with reduced side effects. The pyrazolyl-diamine-functionalized micelles were labeled with fac-[99mTc(CO)3(H2O)3]+ in high radiochemical yield and purity. The radiolabeled micelles are stable in phosphate buffer and in cell culture media. Cellular uptake studies in different cancer cell lines indicate a cell type and time-dependent uptake, in agreement with the anti-proliferative activity. Early biodistribution studies in healthy BALB/c mice has shown prolonged circulation lifetime in the bloodstream and relevant in vivo stability, important features when considering an effective DTX delivery system and image-guided delivery agent for cancer theranostics.
This research was supported by the Fundação para a Ciência e Tecnologia (FCT) through the project EXCL/QEQ-MED/0233/2012 and carried out within European COST actions TD1004. C2TN/IST authors gratefully acknowledge the FCT support through the UID/Multi/04349/2013 project. Elisabete Ribeiro acknowledges the FCT research grant.