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Improved in vivo targeting of BCL-2 phenotypic conversion through hollow gold nanoshell delivery

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Abstract

Although new cancer therapeutics are discovered at a rapid pace, lack of effective means of delivery and cancer chemoresistance thwart many of the promising therapeutics. We demonstrate a method that confronts both of these issues with the light-activated delivery of a Bcl-2 functional converting peptide, NuBCP-9, using hollow gold nanoshells. This approach has shown not only to increase the efficacy of the peptide 30-fold in vitro but also has shown to reduce paclitaxel resistant H460 lung xenograft tumor growth by 56.4%.

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Acknowledgements

This work was supported by the National Institutes of Health (NIH) Grant R01 EB012637 and in part by Grants from the US Army Medical Research and Material Command (W81XWH-08-1-0600 and W81XWH-12-1-0069), American Cancer Society (RSG-13-132-01-CDD), National Institutes of Health (5RO1ES016651) and Oregon State University Venture Development Fund (http://advantage.oregonstate.edu/funding-opportunities). The authors thank support of the NRI Microscopy Center, the Olympus confocal microscope was funded by the NIH Grant 1S10RR022585-01A1. The authors thank A. Mikhailovsky for helpful conversations and aid of the UCSB Optical Characterization Facility. The ultrafast laser system was funded by DURIP ARO Grant 66886LSRIP. The authors would also like to thank former graduate student Demosthenes Morales for helpful discussions.

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Author notes

  1. Erin Morgan and John T. Gamble contributed equally.

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA

    Erin Morgan & Norbert O. Reich

  2. Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA

    John T. Gamble, Martin C. Pearce, Daniel J. Elson, Robert L. Tanguay & Siva Kumar Kolluri

  3. Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA

    Robert L. Tanguay & Siva Kumar Kolluri

  4. Center for Genome Research and Biocomputing, Oregon State University, Corvallis, OR, 97331, USA

    Robert L. Tanguay & Siva Kumar Kolluri

Authors
  1. Erin Morgan
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  2. John T. Gamble
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  3. Martin C. Pearce
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  4. Daniel J. Elson
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  6. Siva Kumar Kolluri
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  7. Norbert O. Reich
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Correspondence to Erin Morgan or Norbert O. Reich.

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Morgan, E., Gamble, J.T., Pearce, M.C. et al. Improved in vivo targeting of BCL-2 phenotypic conversion through hollow gold nanoshell delivery. Apoptosis 24, 529–537 (2019). https://doi.org/10.1007/s10495-019-01531-1

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