三阴性乳腺癌 (TNBC) 可能受益于 PARP 抑制剂 (PARPi)，因为其频繁出现缺陷的同源重组修复 (HR)。然而，PARPi的疗效因其较低的生物利用度和高度耐药性而受到限制，因此常常需要与其他治疗联合使用。在此，构建了聚多巴胺纳米颗粒（PDMN）来负载奥拉帕尼（AZD）作为双通道治疗纳米平台。 PDMN在100 nm左右具有均匀的球形结构，并表现出良好的光热转换效率，达到62.4%。所获得的负载AZD的纳米平台（PDMN-AZD）通过光热疗法（PTT）和PARPi的结合显示出增强的抗肿瘤作用。通过蛋白质印迹和流式细胞术，我们发现PTT和PARPi可以通过进一步增加DNA双链损伤（DSB）和增强HR缺陷来发挥协同抗肿瘤作用。在 BRCA 缺陷小鼠肿瘤模型中观察到 PDMN-AZD 最强的治疗效果。总之，本研究设计的PDMN-AZD纳米平台证明了PTT和PARPi协同治疗TNBC的有效性，并初步解释了其机制。© 2024. Controlled Release Society。

Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.© 2024. Controlled Release Society.