Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma

Inbal Hazkani, Menachem Motiei, Oshra Betzer, Tamar Sadan, Dimitri Bragilovski, Leon Lubimov, Aviram Mizrachi, Tuvia Hadar, Mattan Levi, Irit Ben-Aharon, Izhack Haviv, Rachela Popovtzer*, Aron Popovtzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3962-3971
Number of pages10
JournalTheranostics
Volume7
Issue number16
DOIs
StatePublished - 2017

Keywords

  • Adenoid Cystic Carcinoma
  • Crizotinib
  • Gold nanoparticles
  • Molecular profiling
  • Personalized imaging
  • Radiosensitizing agents

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