Multiple Treatment of Triple-Negative Breast Cancer Through Gambogic Acid-Loaded Mesoporous Polydopamine

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-gamma, IL-6, and TNF-alpha). 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. MPDA serves as a photothermal agent and is proved to be a high-loading carrier for GA. GA acts not only as a cytotoxic drug but also inhibits HSP90, sensitizing photothermal therapy. The GA-loaded MPDA nanoparticles are demonstrated can synergistically inhibit tumor growth, trigger immunogenic cell death, and increase activated effector T cells and inflammatory cytokines, suggesting a promising strategy to enhance the clinical therapeutic effect on TNBC. image