Journal
MATERIALS TODAY BIO
Volume 15, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.mtbio.2022.100316
Keywords
Radiotherapy; Phototherapy; Radiosensitizer; Near-infrared imaging; Heptamethine cyanine dyes
Funding
- National Natural Science Foundation of China [82173457]
- Chongqing Youth Talent Project [cstc2021ycjh-bgzxm0123]
- Outstanding Youth Development Program in Third Military Medical University [AEP17J001]
- Technology Innovation and R&D Projects of Chengdu Science and Technology Bureau [2021-YF05-01659-SN]
- Intramural Research Project Grant [2017]
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A multifunctional small molecule, IR-83, was reported in this study, which can selectively accumulate in tumors, exhibit near-infrared imaging, and have radio/photodynamic/photothermal therapeutic effects. IR-83 targets cancer cell mitochondria, induces excessive ROS generation and high heat, leading to tumor growth suppression and enhanced effectiveness of radiotherapy.
Although as a mainstay modal for cancer treatment, the clinical effect of radiotherapy (RT) does not yet meet the need of cancer patients. Developing tumour-preferential radiosensitizers or combining RT with other treatments has been acknowledged highly necessary to enhance the efficacy of RT. The present study reported a multifunctional bioactive small-molecule (designated as IR-83) simultaneously exhibiting tumour-preferential accumulation, near-infrared imaging and radio/photodynamic/photothermal therapeutic effects. IR-83 was designed and synthesized by introducing 2-nitroimidazole as a radiosensitizer into the framework of heptamethine cyanine dyes inherently with tumour-targeting and photosensitizing effects. As results, IR-83 preferentially accumulated in tumours, suppressed tumour growth and metastasis by integrating radio/photodynamic/photothermal multimodal therapies. Mechanism studies showed that IR-83 accumulated in cancer cell mitochondria, induced excessive reactive oxygen species (ROS), and generated high heat after laser irradiation. On one hand, these phenomena led to mitochondrial dysfunction and a sharp decline in oxidative phosphorylation to lessen tissue oxygen consumption. On the other hand, excessive ROS in mitochondria destroyed the balance of antioxidants and oxidative stress balance by down-regulating the intracellular antioxidant system, and subsequently sensitized ionizing radiation-generated irreversible DNA double-strand breaks. Therefore, this study presented a promising radiosensitizer and a new alternative strategy to enhance RT efficacy via mitochondria-targeting multimodal synergistic treatment.
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