Department of Electrical and Computer Engineering, Boston University, Boston, MA, 02215, USA.
Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Small. 2020 May;16(19):e2001215. doi: 10.1002/smll.202001215. Epub 2020 Apr 20.
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.
用于早期诊断侵袭性前列腺癌的分子探针的开发具有很大的应用前景。在这里，合成了 2-[3-(1,3-二羧基丙基)脲基]戊二酸(DUPA)-缀合配体和双异吲哚基聚合物（BTII），以制定作为前列腺特异性膜抗原（PSMA）靶向探针的半导体聚合物纳米颗粒（BTII-DUPA SPN），用于近红外二区（NIR-II）窗口中的前列腺癌成像。通过瞬态吸收（TA）显微镜和光声（PA）断层扫描技术，获得了从单细胞到整个器官的成像探针与生物靶标相互作用的深入了解。在单细胞水平上，TA 显微镜揭示了 BTII-DUPA SPN 对 PSMA 阳性前列腺癌的靶向效率、动力学和特异性。在器官水平上，BTII-DUPA SPN 在 NIR-II 窗口中的 PA 断层扫描成像显示出优越的成像深度和对比度。通过静脉注射，BTII-DUPA SPN 选择性地在 PSMA 阳性肿瘤中积累和保留，允许通过 PA 检测在体内无创检测 PSMA 过表达的前列腺肿瘤。通过 TA 显微镜进一步分析了纳米颗粒在肿瘤组织内的分布。这些结果共同证明了 BTII-DUPA SPN 是一种有前途的通过 PA 断层扫描术进行前列腺癌诊断的探针。
