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Development of drug-loaded protein nanoparticles displaying enzymatically-conjugated DNA aptamers for cancer cell targeting

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Abstract

Modification of protein-based drug carriers with tumor-targeting properties is an important area of research in the field of anticancer drug delivery. To this end, we developed nanoparticles comprised of elastin-like polypeptides (ELPs) with fused poly-aspartic acid chains (ELP-D) displaying DNA aptamers. DNA aptamers were enzymatically conjugated to the surface of the nanoparticles via genetic incorporation of Gene A* protein into the sequence of the ELP-D fusion protein. Gene A* protein, derived from bacteriophage ϕX174, can form covalent complexes with single-stranded DNA via the latter’s recognition sequence. Gene A* protein-displaying nanoparticles exhibited the ability to deliver the anticancer drug paclitaxel (PTX), whilst retaining activity of the conjugated Gene A* protein. PTX-loaded protein nanoparticles displaying DNA aptamers known to bind to the MUC1 tumor marker resulted in increased cytotoxicity with MCF-7 breast cancer cells compared to PTX-loaded protein nanoparticles without the DNA aptamer modification.

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Acknowledgements

A part of this work was supported by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Life Science and Technology, School of Life Science and Technology and Engineering, Tokyo Institute of Technology, 4259, Midori-ku, Nagatsuta, Yokohama, 226-8502, Japan

    Masayasu Mie, Rie Matsumoto, Yasumasa Mashimo & Eiry Kobatake

  2. Department of Chemistry, Imperial College London, London, W12 0BZ, UK

    Anthony E. G. Cass

Authors
  1. Masayasu Mie
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  2. Rie Matsumoto
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  3. Yasumasa Mashimo
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  4. Anthony E. G. Cass
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  5. Eiry Kobatake
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Correspondence to Eiry Kobatake.

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The authors declare that they have no conflicts of interest.

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Mie, M., Matsumoto, R., Mashimo, Y. et al. Development of drug-loaded protein nanoparticles displaying enzymatically-conjugated DNA aptamers for cancer cell targeting. Mol Biol Rep 46, 261–269 (2019). https://doi.org/10.1007/s11033-018-4467-2

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  • DOI: https://doi.org/10.1007/s11033-018-4467-2

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