Efficient Uptake of 177 Lu-Porphyrin-PEG Nanocomplexes by Tumor Mitochondria for Multimodal-Imaging-Guided Combination Therapy.

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 177 Lu 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 177 Lu-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.

• Authors: Bo Yu, Hao Wei, Qianjun He, Carolina A Ferreira, Christopher J Kutyreff, Dalong Ni, Zachary T Rosenkrans, Liang Cheng, Faquan Yu, Jonathan W Engle, Xiaoli Lan, Weibo Cai
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 57 Issue 1 Pg. 218-222 (01 02 2018) ISSN: 1521-3773 [Electronic] Germany
• PMID: 29092090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Porphyrins
• Radioisotopes
• Polyethylene Glycols
• Lutetium
• Lutetium-177

Topics

• Drug Delivery Systems (methods)
• Humans
• Lutetium (metabolism)
• Mitochondria (metabolism)
• Multimodal Imaging
• Nanoparticles (chemistry)
• Neoplasms (metabolism, radiotherapy, therapy)
• Optical Imaging
• Photochemotherapy (methods)
• Polyethylene Glycols (chemistry)
• Porphyrins (metabolism)
• Positron-Emission Tomography
• Radioisotopes (metabolism)
• Theranostic Nanomedicine (methods)