Theranostics 2017; 7(16):3962-3971. doi:10.7150/thno.19615
Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma
1. Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
2. Head and Neck Cancer Radiation Clinic, Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.
3. Faculty of Engineering & The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Israel
4. Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5. Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel
6. Faculty of Medicine in the Galilee, Bar Ilan University, Ramat Gan, Israel.
Hazkani I, Motiei M, Betzer O, Sadan T, Bragilovski D, Lubimov L, Mizrachi A, Hadar T, Levi M, Ben-Aharon I, Haviv I, Popovtzer R, Popovtzer A. Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma. Theranostics 2017; 7(16):3962-3971. doi:10.7150/thno.19615. Available from http://www.thno.org/v07p3962.htm
Personalized molecular profiling has an established role in selection of treatment for metastatic disease; however, its role in improving radiosensitivity and functional imaging has not been evaluated. In the current study, we examined molecular profiling as a tool for designing personalized targeted gold nanoparticles (GNP) to serve as dual-modal tumor radiosensitizers and functional imaging enhancers. To this end, molecular profiling of a patient's salivary gland adenoid cystic carcinoma (ACC) was performed, and anaplastic lymphoma kinase (ALK) mutation was detected. The extracted tumor was subcutaneously injected into mice, which were then treated either with radiation, the specific ALK inhibitor crizotinib, or a combination of therapies. One of these combinations, namely, ALK-targeted GNP (via crizotinib coating), was found to enhance radiation treatment, as demonstrated by a significant decrease in tumor volume over 24 days. In parallel, ALK-targeted GNP substantially augmented tumor visualization via computed tomography. The mechanism of radiosensitivity enhancement was mostly related to a diminished cell repair mechanism in tumors, as demonstrated by proliferating cell nuclear antigen staining. These findings indicate that personalized molecular profiling is an effective technique for enhancing cancer theranostics.
Keywords: Adenoid Cystic Carcinoma, Gold nanoparticles, crizotinib, molecular profiling, radiosensitizing agents, personalized imaging