文献类型： 会议论文

第一作者： Marta Overchuk

作者： Marta Overchuk ¹ ; Kara M. Harmatys ¹ ; Martha P. F. Damen ¹ ; Juan Chen ² ; Martin G. Pomper ³ ; Gang Zheng ¹ ;

作者机构： 1.Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON, Canada

2.Institute of Biomaterials and Biomedical Engineering, University of Toronto, 101 College Street, Toronto, ON, Canada

3.Johns Hopkins Medical School, 1550 Orleans Street, 492 CRB II, Baltimore, MD 21287, United States

关键词： Photodynamic therapy;bacteriochlorophyll;prostate-specific membrane antigen;PSMA;prostate cancer

会议名称： International Photodynamic Association World Congress

主办单位：

页码： 110704J-1-110704J-6

摘要： 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 (Q_y 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 (Q_y 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.

分类号： N-532