Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA.
Nanoscale. 2021 May 27;13(20):9217-9228. doi: 10.1039/d1nr00669j.
Prostate-specific membrane antigen (PSMA) is a promising diagnostic and therapeutic target for prostate cancer (PC). Poly(amidoamine) [PAMAM] dendrimers serve as versatile scaffolds for imaging agents and drug delivery that can be tailored to different sizes and compositions depending upon the application. We have developed PSMA-targeted PAMAM dendrimers for real-time detection of PC using fluorescence (FL) and photoacoustic (PA) imaging. A generation-4, ethylenediamine core, amine-terminated dendrimer was consecutively conjugated with on average 10 lysine-glutamate-urea PSMA targeting moieties and a different number of sulfo-cyanine7.5 (Cy7.5) near-infrared dyes (2, 4, 6 and 8 denoted as conjugates II, III, IV and V, respectively). The remaining terminal primary amines were capped with butane-1,2-diol functionalities. We also prepared a conjugate composed of Cy7.5-lysine-suberic acid-lysine glutamate-urea (I) and control dendrimer conjugate (VI). Among all conjugates, IV showed superior in vivo target specificity in male NOD-SCID mice bearing isogenic PSMA+ PC3 PIP and PSMA- PC3 flu xenografts and suitable physicochemical properties for FL and PA imaging. Such agents may prove useful in PC cancer detection and subsequent surgical guidance during excision of PSMA-expressing lesions.
前列腺特异性膜抗原（PSMA）是前列腺癌（PC）有前途的诊断和治疗靶点。聚（酰胺-胺）[PAMAM]树枝状大分子可用作成像剂和药物递送的多功能支架，可根据应用的不同大小和组成进行定制。我们已经开发了用于使用荧光（FL）和光声（PA）成像实时检测 PC 的 PSMA 靶向 PAMAM 树枝状大分子。一代 4，乙二胺核心，胺末端树枝状大分子连续与平均 10 个赖氨酸-谷氨酸-脲 PSMA 靶向部分和不同数量的磺基花菁 7.5（Cy7.5）近红外染料（2、4、6 和 8 分别表示为缀合物 II、III、IV 和 V）缀合。其余末端伯胺用丁烷-1,2-二醇官能团封端。我们还制备了由 Cy7.5-赖氨酸-琥珀酸-赖氨酸-谷氨酸-脲（I）和对照树枝状大分子缀合物（VI）组成的缀合物。在所有缀合物中，IV 在携带同基因 PSMA+ PC3 PIP 和 PSMA- PC3 flu 异种移植物的雄性 NOD-SCID 小鼠中表现出优越的体内靶向特异性，并且具有适合 FL 和 PA 成像的理化性质。这些试剂在 PSMA 表达病变切除过程中的 PC 癌检测和随后的手术指导中可能很有用。
