Efficient Uptake of 177Lu‐Porphyrin‐PEG Nanocomplexes by Tumor Mitochondria for Multimodal‐Imaging‐Guided Combination Therapy |
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| Authors: | Dr Bo Yu Dr Hao Wei Prof Qianjun He Carolina A Ferreira Christopher J Kutyreff Dr Dalong Ni Zachary T Rosenkrans Prof Liang Cheng Prof Faquan Yu Prof Jonathan W Engle Prof Xiaoli Lan Prof Weibo Cai |
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| Affiliation: | 1. National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China;2. Departments of Radiology and Medical Physics, University of Wisconsin, Madison, WI, USA;3. Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China;4. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;5. School of Pharmacy, University of Wisconsin, Madison, WI, USA;6. Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, China;7. University of Wisconsin Carbone Cancer Center, Madison, WI, USA |
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| Abstract: | The benefits to intracellular drug delivery from nanomedicine have been limited by biological barriers and to some extent by targeting capability. We investigated a size‐controlled, dual tumor‐mitochondria‐targeted theranostic nanoplatform (Porphyrin‐PEG Nanocomplexes, PPNs). The maximum tumor accumulation (15.6 %ID g?1, 72 h p.i.) and ideal tumor‐to‐muscle ratio (16.6, 72 h p.i.) was achieved using an optimized PPN particle size of approximately 10 nm, as measured by using PET imaging tracing. The stable coordination of PPNs with 177Lu enables the integration of fluorescence imaging (FL) and photodynamic therapy (PDT) with positron emission tomography (PET) imaging and internal radiotherapy (RT). Furthermore, the efficient tumor and mitochondrial uptake of 177Lu‐PPNs greatly enhanced the efficacies of RT and/or PDT. This work developed a facile approach for the fabrication of tumor‐targeted multi‐modal nanotheranostic agents, which enables precision and radionuclide‐based combination tumor therapy. |
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| Keywords: | combination therapy multimodal imaging nanotheranostics radiotherapy targeted delivery |
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