Abstract：
Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.
摘要：
三阴性乳腺癌（TNBC）是一种高度异质性的乳腺癌亚型，具有侵袭性和高复发率。由于单一疗法对TNBC患者的益处有限，联合治疗成为一种有前途的治疗方法。藤黄酸（GA）是一种非常有前途的抗癌剂。尽管如此，低的载药率和相关的毒副作用阻碍了其应用潜力。为了克服这些限制,使用具有光热转化能力的介孔聚多巴胺（MPDA）被认为是GA的递送载体。同时,GA可以抑制热休克蛋白90(HSP90)的活性，增强光热效应。在这里，开发了载GA的MPDA纳米颗粒（GA@MPDANPs），具有75.96％的高载药率和显着的光热转化性能。GA@MPDANPs联合光热治疗(PTT)显著抑制肿瘤生长,并有效触发免疫原性细胞死亡（ICD），从而增加肿瘤中激活的效应T细胞（CD8+T细胞和CD4+T细胞）的数量，并提高免疫炎症细胞因子(IFN-γ，IL-6和TNF-α)。以上结果表明，GA@MPDANPs与PTT的组合有望激活抗肿瘤免疫反应，从而潜在地增强对TNBC的临床治疗效果。
