Mesoporous Bi-Containing Radiosensitizer Loading with DOX to Repolarize Tumor-Associated Macrophages and Elicit Immunogenic Tumor Cell Death to Inhibit Tumor Progression

• DOI: 10.1021/acsami.0c08074
• Publication Date: 2020-06-19T08:48:55Z
• Authors: Xiaojia Qin; Jie Liu; Yunhua Xu; Bing Li; Jingyi Cheng; Xiaodong Wu; Jianping Zhang; Zhengwang Liu; Renli Ning; Yuhao Li; Yingjian Zhang; Yun Sun; Jiade J. Lu
• Keywords: Male; 0301 basic medicine; Radiation-Sensitizing Agents; Lung Neoplasms; THP-1 Cells; CD8-Positive T-Lymphocytes; 3. Good health; Mice; 03 medical and health sciences; Doxorubicin; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Radiation, Ionizing; Tumor-Associated Macrophages; Tumor Microenvironment; Animals; Humans; Bismuth

Tumor-associated macrophages (TAMs) were a major component of tumor, which comprised up to 50% of tumor mass, and correlated with poor prognosis in more than 80% of cases. TAMs were resistant to radiotherapy and chemotherapy, and radiation could further activate TAMs to promote tumor progression. Herein, we explored a kind of Bi-based mesoporous upconversion nanophosphor (UCNP) loaded with doxorubicin (UCNP-DOX) to elicit immunogenic tumor cell death and repolarize TAMs to an antitumor M1-like type for strengthening the tumor-specific antitumor immune effects of X-ray radiotherapy. The repolarization effect of UCNP-DOX with X-ray was confirmed in THP-1 cell line, in vivo mouse model, and hydrothorax of a non-small-cell lung carcinoma patient. Moreover, the UCNP-DOX and X-ray radiation could elicit immunogenic tumor necrosis, presenting more tumor antigens for tumor-specific immune response. In a cell co-incubation system, activated macrophages could significantly inhibit cancer colony formation, migration, and invasion. After treatment, xenografted tumor in mice was also found to be significantly regressed and presented substantial CD8-positive T cells. This study opens the door to further enhance the abscopal effects and inhibit the metastasis in radiotherapy.