前列腺癌 (PC) 是全球男性癌症相关死亡的第五大原因。前列腺特异性膜抗原（PSMA）是PC的分子靶标，临床上通过放射性配体方法用于治疗和诊断PC。然而，FDA 尚未批准基于 PSMA 的化疗。在这里，我们提出了一种新的治疗方法，使用 PSMA 靶向 2-脱氧葡萄糖树枝状聚合物 (PSMA-2DG-D) 选择性地将有效的酪氨酸激酶抑制剂卡博替尼 (Cabo) 靶向递送至 PC 细胞。 PSMA-2DG-D 证明通过 PSMA 介导的内化在 PSMA ( ) PC 细胞中进行细胞内定位。当与 PSMA-2DG-D 结合时，与游离药物相比，这种 PSMA 特异性靶向转化为 Cabo 的功效增强。此外，全身施用荧光标记的 PSMA-2DG-D-Cy5 特异性靶向 PSMA ( ) 肿瘤，在 PC3-PIP 肿瘤异种移植小鼠模型中脱靶积累最小。这表明 PSMA-2DG-D 平台是一种有前途的新型强效化疗药物递送系统，其中全身副作用是一个重大问题。

Prostate cancer (PC) is the fifth leading cause of cancer-related deaths among men worldwide. Prostate-specific membrane antigen (PSMA), a molecular target of PC, is clinically used for the treatment and diagnosis of PC using radioligand approaches. However, no PSMA-based chemotherapies have yet been approved by the FDA. Here, we present a novel therapeutic approach using PSMA-targeted 2-deoxyglucose-dendrimer (PSMA-2DG-D) for targeted delivery of a potent tyrosine kinase inhibitor, cabozantinib (Cabo), selectively to PC cells. PSMA-2DG-D demonstrates intracellular localization in PSMA (+) PC cells through PSMA-mediated internalization. This PSMA-specific targeting translates to enhanced efficacy of Cabo compared to the free drug when conjugated to PSMA-2DG-D. Furthermore, systemically administered fluorescently labeled PSMA-2DG-D-Cy5 specifically targets PSMA (+) tumors with minimal off-target accumulation in the PC3-PIP tumor xenograft mouse model. This demonstrates that the PSMA-2DG-D platform is a promising new delivery system for potent chemotherapeutics, where systemic side effects are a significant concern.