Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors

  • Commun Biol. 2020 May 8;3(1):226. doi: 10.1038/s42003-020-0956-7.
Kensuke Kaneko  1 ,  Takuya Osada  1 ,  Michael A Morse  1  2 ,  William R Gwin  3 ,  Joshua D Ginzel  4 ,  Joshua C Snyder  1  4 ,  Xiao-Yi Yang  1 ,  Cong-Xiao Liu  1 ,  Márcio A Diniz  5 ,  Khaldon Bodoor  6 ,  Philip F Hughes  6 ,  Timothy Aj Haystead  7 ,  H Kim Lyerly  8
Affiliations
  • 1. Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.
  • 2. Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
  • 3. Department of Medicine, University of Washington, Seattle, WA, 98195, USA.
  • 4. Department of Cell Biology, Duke University, Durham, NC, 27710, USA.
  • 5. Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • 6. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, 27710, USA.
  • 7. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, 27710, USA. [email protected].
  • 8. Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA. [email protected].
PMID: 32385408 DOI: 10.1038/s42003-020-0956-7
Abstract

Photodynamic therapy (PDT) ablates malignancies by applying focused near-infrared (nIR) light onto a lesion of interest after systemic administration of a Photosensitizer (PS); however, the accumulation of existing PS is not tumor-exclusive. We developed a tumor-localizing strategy for PDT, exploiting the high expression of heat shock protein 90 (HSP90) in Cancer cells to retain high concentrations of PS by tethering a small molecule HSP90 Inhibitor to a PS (verteporfin, VP) to create an Hsp90-targeted PS (HS201). HS201 accumulates to a greater extent than VP in breast Cancer cells both in vitro and in vivo, resulting in increased treatment efficacy of HS201-PDT in various human breast Cancer xenografts regardless of molecular and clinical subtypes. The therapeutic index achieved with Hsp90-targeted PDT would permit treatment not only of localized tumors, but also more diffusely infiltrating processes such as inflammatory breast Cancer.

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