Long ‐Circulating Prostate‐Specific Membrane Antigen‐Targeted NIR Phototheranostic Agent

AbstractTargeted photodynamic therapy (PDT) combined with image ‐guided surgical resection is a promising strategy for precision cancer treatment. Prostate‐specific membrane antigen (PSMA) is an attractive target due to its pronounced overexpression in a variety of tumours, most notably in prostate cancer. Recently, we reported a pyropheophorbide‐based PSM A‐targeted agent, which exhibited long plasma circulation time and effective tumor accumulation. To further advance PSMA‐targeted photodynamic therapy by harvesting tissue‐penetrating properties of the NIR light, we developed a bacteriochlorophyll‐based PSMA‐targeted photosensitizer (BPP), consisting of three building blocks: 1) a PSMA‐affinity ligand, 2) a peptide linker to prolong plasma circulation time, and 3) a bacteriochlorophyll photosensitizer for NIR fluorescence imaging and photodynamic therapy (Qy absorption maximum at 750 nm). BPP exhibited excellent PSMA targeting sele ctivity in both subcutaneous and orthotopic mouse models. The nine D‐peptide linker in BPP structure prolonged its plasma circulation time (12.65 hours). Favorable pharmacokinetic properties combined with excellent targeting selectivity enabled effective BPP tumor accumulation, which led to effect ive PDT in a subcutaneous prostate adenocarcinoma mouse model. Overall, bright NIR fluorescence of BPP enables effective image guidance for surgical resection, while the combination of its targeting capabilities and PDT activity allo...
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: Research Note Source Type: research