@inproceedings{deea091236e74677821b596c3e825aea,
title = "Long-circulating prostate-specific membrane antigen-targeted NIR phototheranostic agent",
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.",
keywords = "Bacteriochlorophyll, PSMA, Photodynamic therapy, Prostate cancer, Prostate-specific membrane antigen",
author = "Marta Overchuk and Harmatys, {Kara M.} and Damen, {Martha P.F.} and Juan Chen and Pomper, {Martin G.} and Gang Zheng",
note = "Funding Information: The authors would like to acknowledge Lili Ding, Deborah Scollard and Teesha Komal for technical assistance. This study was funded by the Terry Fox Research Institute (PPG#1075), the Canadian Institute of Health Research (Foundation Grant #154326), the Vanier Canada Graduate Scholarship, the Canada Foundation for Innovation (no. 21765), the Natural Sciences and Engineering Research Council of Canada (no. 386613) and the Princess Margaret Cancer Foundation. Funding Information: The authors would like to acknowledge Lili Ding, Deborah Scollard and Teesha Komal for technical assistance. This study was funded by the Terry Fox Research Institute (PPG#1075), the Canadian Institute of Health Research (Foundation Grant #154326), the Vanier Canada Graduate Scholarship, the Canada Foundation for Innovation (no. 21765), the Natural SciencesandEngineeringResearchCouncilofCanada(no.386613)andtherPicness Margaret CanceroFundation. Publisher Copyright: {\textcopyright} 2019 SPIE.; 17th International Photodynamic Association World Congress 2019 ; Conference date: 28-06-2019 Through 04-07-2019",
year = "2019",
doi = "10.1117/12.2525622",
language = "English (US)",
series = "Proceedings of SPIE - The International Society for Optical Engineering",
publisher = "SPIE",
editor = "Tayyaba Hasan",
booktitle = "17th International Photodynamic Association World Congress",
}