Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 1, Pages 218-222Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201710232
Keywords
combination therapy; multimodal imaging; nanotheranostics; radiotherapy; targeted delivery
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Funding
- National Natural Science Foundation of China [81601605, 21571147]
- Postdoctoral Science Foundation of China [2016M600670]
- University of Wisconsin-Madison
- National Institutes of Health [P30CA014520]
- American Cancer Society [125246-RSG-13-099-01-CCE]
- Natural Science Foundation of SZU [827-000143]
- Shenzhen Peacock Plan [KQTD2016053112051497]
- Shenzhen Basic Research Program [JCYJ20170302151858466]
- NATIONAL CANCER INSTITUTE [P30CA014520] Funding Source: NIH RePORTER
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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 Lu-177 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 Lu-177-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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