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Preparation of pyrenyl-based multifunctional nanocomposites for biomedical applications

Abstract

Nanocomposites are widely used to obtain an accurate diagnosis of, and to provide effective therapy for, a number of diseases, because they can be easily formulated by introducing therapeutic agents (e.g., drugs and genes) and imaging agents (e.g., magnetic nanocrystals). Furthermore, nanocomposites can be developed as all-in-one systems, which enable cancer diagnosis and therapy, as well as the simultaneous monitoring of drug behavior. In this protocol, we describe the synthesis of four pyrenyl-based polymers (pyrenyl polyethylene glycol (Py-PEG), pyrenyl dextran (Py-DEX), pyrenyl hyaluronan (Py-HA) and pyrenyl-conjugated heterofunctional PEG (pyrenyl PEG)) and their subsequent use in the preparation of multifunctional nanocomposites for different applications including multimodal imaging, targeted cancer detection and pH-sensitive drug delivery. Notably, these nanocomposites can be used to simultaneously perform multiple tasks—for example, delivering magnetic particles for early cancer detection by MRI, efficient cataloging of patient groups for personalized therapy and real-time monitoring of disease progress. Starting from the synthesis of pyrenyl-based polymers, this protocol can be completed in 15 d.

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Figure 1: Schematic illustration of multifunctional nanocomposites.
Figure 2
Figure 3
Figure 4: Characterization of pyrenyl-based polymers.
Figure 5: Characterization of magnetic nanoparticles.
Figure 6: Characterization of fluorescent magnetic nanocomposites.
Figure 7: Comparative analysis of the magnetic properties of magnetic nanoparticles and of fluorescent magnetic nanocomposites.
Figure 8: Characteristics of magnetic nanocomposites.
Figure 9: Additional characterization data on magnetic nanocomposites.
Figure 10: Characterization of magnetic nanocomposites for breast cancer–targeted MRI.
Figure 11: In vitro tests of magnetic nanocomposites.
Figure 12: Characterization of drug carriers.
Figure 13: Activity profiles of drug carriers.
Figure 14: Characterization of theranostic nanocomposites.
Figure 15: Activity analysis of theranostic nanocomposites.

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Acknowledgements

This study was supported by a grant from the BioNano Health Guard Research Center funded by the Ministry of Science, ICT and Future Planning (MSIP) of Korea as a Global Frontier Project (H-GUARD_2013 M3A6B2078950), National Research Foundation of Korea (NRF) funded by the Ministry of Education Science and Technology (NRF-2012R1A1A2043991; NRF-2014M3A6B2060507) and KRIBB Research Initiative Program.

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E.-K.L. conceived and wrote this paper. E.-K.L. and B.H.C. revised the paper.

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Correspondence to Bong Hyun Chung.

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Lim, EK., Chung, B. Preparation of pyrenyl-based multifunctional nanocomposites for biomedical applications. Nat Protoc 11, 236–251 (2016). https://doi.org/10.1038/nprot.2015.135

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