Long-circulating prostate-specific membrane antigen-targeted NIR phototheranostic agent

Marta Overchuk, Kara M. Harmatys, Martha P.F. Damen, Juan Chen, Martin G. Pomper, Gang Zheng

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Targeted photodynamic therapy (PDT) combined with image-guided surgical resection is a promising strategy for precision cancer treatment. Targeting the prostate-specific membrane antigen (PSMA) has drawn significant attention due to its marked overexpression in a variety of malignant tissues, most notably in prostate cancer. Recently, we reported the design of a pyropheophorbide-based long-circulating PSMA-targeted phototheranostic agent for multimodal PET/fluorescence imaging and potent PDT of prostate cancer. While this agent is effective in a subcutaneous mouse model, the non-optimal optical properties of pyropheophorbide (Qy absorption maximum at 671 nm) pose a limitation for treatment of deep-seated solid tumors. To further advance PSMA-targeted PDT and enable effective treatment to the deeper layers of tumor tissue, we developed a bacteriochlorophyll-based PSMA-targeted photosensitizer (BPP) which consists of three building blocks: 1) a urea-based PSMA-affinity ligand, 2) a peptide linker to prolong plasma circulation time, and 3) a bacteriochlorophyll photosensitizer for NIR fluorescence imaging (Qy absorption maximum at 750 nm). BPP demonstrated effective cell internalization as well as PDT activity in PSMA-expressing PC3-PIP cells. Furthermore, this agent possesses excellent targeting selectivity in vivo as demonstrated in a dual PSMA-positive and PSMA-negative subcutaneous tumor model. The peptide linker in BPP allowed for its long plasma circulation time (12.65 hours), which enabled its effective tumor accumulation. Overall, bright NIR fluorescence of BPP enables effective image guidance for surgical resection, while the combination of its superb targeting and strong PDT activity allows for potent and precise photodynamic treatment of deep-seated tumors.

Original languageEnglish (US)
Title of host publication17th International Photodynamic Association World Congress
EditorsTayyaba Hasan
PublisherSPIE
ISBN (Electronic)9781510628335
DOIs
StatePublished - Jan 1 2019
Event17th International Photodynamic Association World Congress 2019 - Cambridge, United States
Duration: Jun 28 2019Jul 4 2019

Publication series

NameProceedings of SPIE - The International Society for Optical Engineering
Volume11070
ISSN (Print)0277-786X
ISSN (Electronic)1996-756X

Conference

Conference17th International Photodynamic Association World Congress 2019
CountryUnited States
CityCambridge
Period6/28/197/4/19

Keywords

  • Bacteriochlorophyll
  • Photodynamic therapy
  • Prostate cancer
  • Prostate-specific membrane antigen
  • PSMA

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Computer Science Applications
  • Applied Mathematics
  • Electrical and Electronic Engineering

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  • Cite this

    Overchuk, M., Harmatys, K. M., Damen, M. P. F., Chen, J., Pomper, M. G., & Zheng, G. (2019). Long-circulating prostate-specific membrane antigen-targeted NIR phototheranostic agent. In T. Hasan (Ed.), 17th International Photodynamic Association World Congress [110704J] (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 11070). SPIE. https://doi.org/10.1117/12.2525622