Functionalized NIR-II Semiconducting Polymer Nanoparticles for Single-cell to Whole-Organ Imaging of PSMA-Positive Prostate Cancer

Development of molecular probes holds great promise for early diagnosis of aggressive prostate cancer. Here, 2-[3-(1,3-dicarboxypropyl) ureido] pentanedioic acid (DUPA)-conjugated ligand and bis-isoindigo-based polymer (BTII) are synthesized to formulate semiconducting polymer nanoparticles (BTII-DUPA SPN) as a prostate-specific membrane antigen (PSMA)-targeted probe for prostate cancer imaging in the NIR-II window. Insights into the interaction of the imaging probes with the biological targets from single cell to whole organ are obtained by transient absorption (TA) microscopy and photoacoustic (PA) tomography. At single-cell level, TA microscopy reveals the targeting efficiency, kinetics, and specificity of BTII-DUPA SPN to PSMA-positive prostate cancer. At organ level, PA tomographic imaging of BTII-DUPA SPN in the NIR-II window demonstrates superior imaging depth and contrast. By intravenous administration, BTII-DUPA SPN demonstrates selective accumulation and retention in the PSMA-positive tumor, allowing noninvasive PA detection of PSMA overexpressing prostate tumors in vivo. The distribution of nanoparticles inside the tumor tissue is further analyzed through TA microscopy. These results collectively demonstrate BTII-DUPA SPN as a promising probe for prostate cancer diagnosis by PA tomography.