Nanoparticle formulation of small DNA molecules, Dbait, improves the sensitivity of hormone-independent prostate cancer to radiotherapy.

Intensification of radiotherapy has been shown to improve prostate cancer (PCa) outcomes. We hypothesized that we could further improve radiotherapy efficacy through the use DNA repair inhibitors. In this study, we evaluated the use of a new class of DNA damage repair inhibitor, nanoparticle (NP) Dbait, in radiosensitization of PCa. NP Dbait was formulated using H1 nanopolymer (folate-polyethylenimine600-cyclodextrin). We demonstrated that NP Dbait was a potent radiosensitizer in vitro by colony forming assay using PCa cell lines. The result was validated in vivo using mouse xenograft models of PCa and we showed that NP Dbait significantly suppressed tumor growth and prolonged survival. Western blot, immunofluorescence and immunohistochemistry showed that NP Dbait inhibited DNA damage repair signaling pathways by mimicking DNA double-strand breaks. Our study supports further investigations of NP Dbait in improving the therapeutic efficacy of cancer radiotherapy.