1. School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China;
2. State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China;
3. College of Chemistry and Environment Protection Engineering, Southwest Minzu University, Chengdu 610041, China;
4. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
* Equal contribution
Nanotechniques that can improve the effectiveness of radiotherapy (RT) by integrating it with multimodal imaging are highly desirable.
Results In this study, we fabricated Bi2S3 nanorods that have attractive features such as their ability to function as contrast agents for X-ray computed tomography (CT) and photoacoustic (PA) imaging as well as good biocompatibility. Both in vitro and in vivo studies confirmed that the Bi2S3 nanoagents could potentiate the lethal effects of radiation via amplifying the local radiation dose and enhancing the anti-tumor efficacy of RT by augmenting the photo-thermal effect. Furthermore, the nanoagent-mediated hyperthermia could effectively increase the oxygen concentration in hypoxic regions thereby inhibiting the expression of hypoxia-inducible factor (HIF-1α). This, in turn, interfered with DNA repair via decreasing the expression of DNA repair-related proteins to overcome radio-resistance. Also, RT combined with nanoagent-mediated hyperthermia could substantially suppress tumor metastasis via down-regulating angiogenic factors.
Conclusion In summary, we constructed a single-component powerful nanoagent for CT/PA imaging-guided tumor radiotherapy and, most importantly, explored the potential mechanisms of nanoagent-mediated photo-thermal treatment for enhancing the efficacy of RT in a synergistic manner.
Keywords: multimodal imaging, radiation therapy, hypoxia, DNA repair, synergistic therapy.