Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor

Journal of Nanobiotechnology

Liang Zhang¹  Tingting Shang¹  Pan Li¹  Zhigang Wang¹  Di Zhou²  Jiexin Wen³  Hui Gao³  Zhaoxia Wang³  Dong Wang⁴  Yong Luo⁵  Xiang Wang⁶  Ju Huang⁶ 

[1] Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, 400010, Chongqing, People’s Republic of China;Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, 400042, Chongqing, People’s Republic of China;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, 400014, Chongqing, People’s Republic of China;Department of Ultrasound, The First Affiliated Hospital, Chongqing Medical University, 400042, Chongqing, People’s Republic of China;Department of Ultrasound, The First People’s Hospital of Chongqing Liang Jiang New Area, 401121, Chongqing, People’s Republic of China;Department of Ultrasound, The Third Affiliated Hospital, Chongqing Medical University, 401120, Chongqing, People’s Republic of China;

关键词: Hypoxic tumor;    3-Bromopyruvate;    Respiration inhibition;    Photodynamic therapy;    Nanomedicine;   

DOI  :  10.1186/s12951-021-01196-6

来源: Springer

【 摘 要 】

BackgroundPhotodynamic 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.ResultsThe 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.ConclusionsThis 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.Graphical Abstract

【 授权许可】

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