1. Academic Validation
  2. Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors

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

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].
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.

Figures
Products