International Journal of Nanomedicine (Oct 2021)
Immunogenic Cell Death Induced by Chemoradiotherapy of Novel pH-Sensitive Cargo-Loaded Polymersomes in Glioblastoma
Abstract
Chen He,1 Huiyan Ding,1 Jing Chen,1 Yinan Ding,1 Rui Yang,2 Chunmei Hu,3 Yanli An,1 Dongfang Liu,1 Peidang Liu,1 Qiusha Tang,1 Zhiyuan Zhang4 1Medical School of Southeast University, Nanjing, People’s Republic of China; 2Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Tuberculosis, The Second Affiliated Hospital of Southeast University (The Second Hospital of Nanjing), Nanjing, People’s Republic of China; 4Department of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Qiusha TangMedical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, People’s Republic of ChinaEmail [email protected] ZhangDepartment of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, People’s Republic of ChinaEmail [email protected]: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously, a new type of pH-sensitive polymersome was designed for the treatment of glioblastoma which represents a promising nanoplatform for future translational research in glioblastoma therapy. In this study, the aim of this work was to analyse whether chemoradiotherapy of the novel pH-sensitive cargo-loaded polymersomes can induce ICD.Methods: Cell death in U87-MG and G422 cells was induced by Au-DOX@PO-ANG, and cell death was analysed by CCK-8 and flow cytometry. The release of CRT was determined by using laser scanning confocal microscopy and flow cytometry. ELISA kits were used to detect the release of HMGB1 and ATP. The dying cancer cells treated with different treatments were cocultured with bone-marrow-derived dendritic cells (BMDCs), and then flow cytometry was used to determine the maturation rate of BMDCs (CD11c+CD86+CD80+) to analyse the in vitro immunogenicity. Tumour vaccination experiments were used to evaluate the ability of Au-DOX@PO-ANG to induce ICD in vivo.Results: We determined the optimal treatment strategy to evaluate the ability of chemotherapy combined with radiotherapy to induce ICD and dying cancer cells induced by Au-DOX@PO-ANG+RT could induce calreticulin eversion to the cell membrane, promote the release of HMGB1 and ATP, and induce the maturation of BMDCs. Using dying cancer cells induced by Au-DOX@PO-ANG+RT, we demonstrate the efficient vaccination potential of ICD in vivo.Conclusion: These results identify Au-DOX@PO-ANG as a novel immunogenic cell death inducer in vitro and in vivo that could be effectively combined with RT in cancer therapy.Keywords: immunogenic cell death, ICD, glioblastoma, radiotherapy, polymersomes, nanodrug delivery system
