Jiexin Wen1, Yong Luo2, Hui Gao1, Liang Zhang3, Xiang Wang4, Ju Huang4, Tingting Shang3, Di Zhou5, Dong Wang6, Zhigang Wang3, Pan Li3, Zhaoxia Wang7. 1. Department of Ultrasound, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China. 2. Department of Ultrasound, The First People's Hospital of Chongqing Liang Jiang New Area, Chongqing, 401121, People's Republic of China. 3. Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, People's Republic of China. 4. Department of Ultrasound, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 401120, People's Republic of China. 5. Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400042, People's Republic of China. 6. Department of Ultrasound, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400042, People's Republic of China. 7. Department of Ultrasound, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China. zhaoxia_wang103@163.com.
Abstract
BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.
BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.
Authors: Shunhao Wang; Lu Shang; Linlin Li; Yingjie Yu; Chongwei Chi; Kun Wang; Jie Zhang; Run Shi; Heyun Shen; Geoffrey I N Waterhouse; Sijin Liu; Jie Tian; Tierui Zhang; Huiyu Liu Journal: Adv Mater Date: 2016-07-27 Impact factor: 30.849
Authors: Ana Paula Pereira da Silva; Tatiana El-Bacha; Nattascha Kyaw; Reinaldo Sousa dos Santos; Wagner Seixas da-Silva; Fabio C L Almeida; Andrea T Da Poian; Antonio Galina Journal: Biochem J Date: 2009-02-01 Impact factor: 3.857