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Outline
Triple-negative breast cancer (TNBC) is characterized by high invasiveness, a high risk of recurrence and metastasis, and poor prognosis. The accumulation of lactate in the tumor microenvironment produced by tumor cell glycolysis is a key factor driving the malignant progression of TNBC. In this study, we developed a lactate metabolism-regulating self-assembled galloflavin-Fe lipid peroxidation accelerator (SGF) to inhibit the growth of TNBC. The system was constructed by coordinating iron ions with the hydroxyl groups of galloflavin to form a metal-polyphenol network, which encapsulates the drug sorafenib. By adjusting the drug loading ratio of sorafenib to galloflavin at 1:1, SGF nanoparticles with a size of 136.20 ± 0.83 nm and a polydispersity index of 0.103 ± 0.012 were prepared, achieving efficient co-loading of both drugs. The metal-polyphenol network of SGF exhibits photothermal conversion properties, generating localized heat under 808 nm laser irradiation, effectively killing tumor cells. Under the low pH conditions of the tumor microenvironment and lysosomes, iron ions and galloflavin dissociate to release sorafenib, accelerating the Fenton reaction through iron ion supplementation and glutathione downregulation, which cooperatively promotes lipid peroxidation in tumor cells. Furthermore, galloflavin inhibits lactate dehydrogenase A, downregulating the conversion of pyruvate to lactate and reducing lactate production, thereby improving the acidic tumor microenvironment and efficiently suppressing the progression of TNBC. The SGF nanosystem designed and constructed in this study integrates three synergistic mechanisms-photothermal effect, lipid peroxidation induction, and lactate metabolism regulation to provide a synergistic and precise strike against TNBC and its high-lactate microenvironment, offering a new therapeutic strategy to improve the clinical prognosis of this highly invasive cancer.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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