Abstract
Virus-like particles (VLPs) have emerged as important and versatile architectures for chemical manipulation in the development of functional hybrid nanostructures. Here we demonstrate a successful site-selective initiation of atom-transfer radical polymerization reactions to form an addressable polymer constrained within the interior cavity of a VLP. Potentially, this protein–polymer hybrid of P22 and cross-linked poly(2-aminoethyl methacrylate) could be useful as a new high-density delivery vehicle for the encapsulation and delivery of small-molecule cargos. In particular, the encapsulated polymer can act as a scaffold for the attachment of small functional molecules, such as fluorescein dye or the magnetic resonance imaging (MRI) contrast agent Gd-diethylenetriaminepentacetate, through reactions with its pendant primary amine groups. Using this approach, a significant increase in the labelling density of the VLP, compared to that of previous modifications of VLPs, can be achieved. These results highlight the use of multimeric protein–polymer conjugates for their potential utility in the development of VLP-based MRI contrast agents with the possibility of loading other cargos.
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Acknowledgements
This research was supported in part by grants from the National Institutes of Health (R01-EB012027), the National Science Foundation (CBET-0709358) and a National Science Foundation Graduate Research Fellowship (J.L.). P.E.P. and G.J.B. were supported by the US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering (DE-FG02-08ER46537).
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J.L. designed and carried out the experiments. S.Q. characterized the samples by NMR and analysed the relaxivity data. M.U. and B.L.F. assisted in the initial characterization of the S39C mutant. G.J.B. characterized the samples by analytical ultracentrifugation. M.U. and T.D. assisted in the experimental design. J.L. and T.D. co-wrote the manuscript. P.E.P. and T.D. coordinated the project. All authors discussed the results.
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Lucon, J., Qazi, S., Uchida, M. et al. Use of the interior cavity of the P22 capsid for site-specific initiation of atom-transfer radical polymerization with high-density cargo loading. Nature Chem 4, 781–788 (2012). https://doi.org/10.1038/nchem.1442
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DOI: https://doi.org/10.1038/nchem.1442
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