Galectin-1-based tumor-targeting for gold nanostructure mediated theranostics
by Jenkins, Samir; Nedosekin, Dmitry; Dings, Ruud; Chen, Jingyi; Griffin, Robert
Anginex (Ax) is an antiangiogenic, synthetic 33mer that binds to galectin-1, which is overexpressed by the tumor endothelium- a crit. requirement for effective nanomedicine delivery- as well as tumor cells themselves. In the present study, Ax was used as a targeting agent after conjugation to polydopamine-coated Au nanocages, selected for their photothermal conversion, biocompatibility and functionalization potential. The retention of Ax's biol. activity was confirmed through migration assays and tube formation assays, and untargeted Au nanocages did not demonstrate an effect. Targeting was confirmed by darkfield microscopy, photoacoustic microscopy, photoacoustic flow cytometry, which showed that Ax significantly increased the binding with the cell surface. However, as expected from our previous studies demonstrating that Ax at these levels has negligible effect on cell viability, we obsd. that conjugated and unconjugated nanocages had an ED50 greater than 100 pM in std. proliferation assays. In contrast, we found that combining 25 pM conjugated nanocages and 10 min near IR irradn. induced photothermal therapeutic effects resulting in marked cell death for both tumor and endothelial cells in vitro. Addnl. these targeted Au nanocages were shown to be able to function as a radiosensitizer, reducing clonal survival to one fourth of radiation alone and one half relative to untargeted cages. Ax further enabled these nanocages to specifically target tumor tissue, significantly increasing the accumulation/retention in tumors relative to untargeted cages; accumulation of targeted nanocages was also obsd. to increase in spleen, and liver. Notably, i.v. injection of a dose of 50 pmol/kg resulted in no obsd. adverse toxicity over 3 days. Photoacoustic detection of particles was further employed to det. the pharmacokinetic profile, and the particles were found to continue circulating for more than two hours, with gradual increases in tumor accumulation. The in vivo photothermal capacity of the construct was characterized. Multiplexing this thermal treatment with addnl. therapies, particular chemotherapy and radiation, is currently under investigation using in vivo models of breast and lung cancer.