| Summary: | Min Wu,1,* Jing Liu,1,* ChuanFei Hu,1 Dong Li,1 Juan Yang,1 ZhouXue Wu,1 LingLin Yang,1 Yue Chen,2 ShaoZhi Fu,1 JingBo Wu1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China *These authors contributed equally to this work Background: Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair process of DNA strand breaks (DSBs). Olaparib (Ola) is a PARP inhibitor that is involved in arresting PARP release from radiotherapy (RT)-induced damaged DNA to potentiate the effect of RT. Although the underlying mechanisms for the radiosensitization effects of Ola are well understood in vitro, the radiosensitization effects in vivo are still unclear. Moreover, poor water solubility and severe toxicity are two major impediments for the clinical success of Ola.Materials and methods: Here, we developed olaparib nanoparticles (Ola-NPs) and investigated their radiosensitization mechanisms and toxicity using human non-small-cell lung cancer xenograft models in mice.Results: The prepared Ola-NPs showed a mean size of 31.96±1.54 nm and a lower polydispersity index of about 0.126±0.014. In addition, the sensitization enhancement ratio of Ola-NPs (3.81) was much higher than that of free Ola (1.66). The combination of Ola-NPs and RT (Ola-NPs + RT) significantly inhibited tumor growth and prolonged survival in mice. The mechanism of enhanced antitumor efficacy might be related to the inhibition of DSB repair and the promotion of cell apoptosis in vivo. No additional toxicity caused by Ola-NPs was observed.Conclusion: This study demonstrated the principle of using Ola-NPs as a potent radiosensitizer to improve the therapeutic effect of RT relative to free Ola (P<0.05 in all cases). Keywords: lung cancer, nanoparticles, olaparib, radiosensitization
|
|---|
