Zhenyu Hou1, Mei Zhou1, Yuanyuan Ma1, Xiaoxuan Xu1, Zhiqi Zhang1, Shiwei Lai1, Wenpei Fan2, Jinbing Xie3,4, Shenghong Ju5. 1. Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. 2. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. 3. Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. xiejb@seu.edu.cn. 4. State Key Laboratory of Bioelectronics, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. xiejb@seu.edu.cn. 5. Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. jsh@seu.edu.cn.
Abstract
PURPOSE: Radiation therapy (RT) and photodynamic therapy (PDT) are promising while challenging in treating tumors. The potential radiation resistance of tumor cells and side effects to healthy tissues restrict their clinical treatment efficacy. Effective delivery of therapeutic agents to the deep tumor tissues would be available for tumor-accurate therapy and promising for the tumor therapy. Thus, developing nanoprobes with effectively delivering radiotherapy sensitizers and photosensitizers to the interior of tumors is needed for the accurate combined RT and PDT of tumor. METHODS: The size-changeable nanoprobes of Gd2O3@BSA-BSA-Ce6 (BGBC) were synthesized with a crosslinking method. Magnetic resonance imaging (MRI) and in vivo near-infrared (NIR) imaging were measured to evaluate the nanoprobes' tumor accumulation and intratumor penetration effect. The tumor suppression effect of combined RT and PDT with these nanoprobes was also studied for the 4T1 bearing Balb/c mice. RESULTS: The nanoprobes BGBC showed high tumor accumulation and disintegrated into small particles responding to the photo-irradiation-produced reactive oxygen species (ROS), allowing for tumor penetration. Abundant radiotherapy sensitizers and photosensitizers were delivered to the deep tumor tissues, which is available for the accurate therapy of tumor. In addition, the BGBC displayed outstanding MRI and fluorescence imaging effects for evaluating the biodistribution and tumor suppression effect of nanoprobes. Consequently, significant tumor suppression effect was obtained based on the accurate tumor treatment with the combined RT and PDT. CONCLUSION: The designed size-changeable nanoprobes BGBC showed excellent tumor accumulation and deep tumor penetration, resulting in a significant tumor suppression effect based on the combined RT and PDT. This study provides a novel strategy for dual delivery of radiotherapy sensitizers and photosensitizers into the deep tumor tissues and is promising for the accurate theranostics of tumor.
PURPOSE: Radiation therapy (RT) and photodynamic therapy (PDT) are promising while challenging in treating tumors. The potential radiation resistance of tumor cells and side effects to healthy tissues restrict their clinical treatment efficacy. Effective delivery of therapeutic agents to the deep tumor tissues would be available for tumor-accurate therapy and promising for the tumor therapy. Thus, developing nanoprobes with effectively delivering radiotherapy sensitizers and photosensitizers to the interior of tumors is needed for the accurate combined RT and PDT of tumor. METHODS: The size-changeable nanoprobes of Gd2O3@BSA-BSA-Ce6 (BGBC) were synthesized with a crosslinking method. Magnetic resonance imaging (MRI) and in vivo near-infrared (NIR) imaging were measured to evaluate the nanoprobes' tumor accumulation and intratumor penetration effect. The tumor suppression effect of combined RT and PDT with these nanoprobes was also studied for the 4T1 bearing Balb/c mice. RESULTS: The nanoprobes BGBC showed high tumor accumulation and disintegrated into small particles responding to the photo-irradiation-produced reactive oxygen species (ROS), allowing for tumor penetration. Abundant radiotherapy sensitizers and photosensitizers were delivered to the deep tumor tissues, which is available for the accurate therapy of tumor. In addition, the BGBC displayed outstanding MRI and fluorescence imaging effects for evaluating the biodistribution and tumor suppression effect of nanoprobes. Consequently, significant tumor suppression effect was obtained based on the accurate tumor treatment with the combined RT and PDT. CONCLUSION: The designed size-changeable nanoprobes BGBC showed excellent tumor accumulation and deep tumor penetration, resulting in a significant tumor suppression effect based on the combined RT and PDT. This study provides a novel strategy for dual delivery of radiotherapy sensitizers and photosensitizers into the deep tumor tissues and is promising for the accurate theranostics of tumor.