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Abstract：
Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.
摘要：
尽管几种人工纳米疗法已被批准用于转移性乳腺癌的实际治疗，他们低效的治疗结果，严重的不良影响,大规模生产的高成本仍然是关键的挑战。在这里，我们开发了一种替代策略,通过使用来自茶花的天然纳米载体(TFEN)特异性触发乳腺肿瘤细胞凋亡并抑制其肺转移.这些纳米载体具有理想的粒径（131nm），外泌体样形态，和负zeta电位。此外，TFEN被发现含有大量的多酚，黄酮类化合物，功能蛋白,和脂质。细胞实验表明，由于刺激活性氧（ROS）扩增，TFEN对癌细胞显示出强细胞毒性。细胞内ROS数量的增加不仅可以触发线粒体损伤，但也阻止细胞周期，导致体外抗增殖，反移民,和抗乳腺癌细胞侵袭活性。进一步的小鼠研究表明，静脉内（i.v.）注射或口服给药后的TFEN可以在乳腺肿瘤和肺转移部位积聚，抑制乳腺癌的生长和转移，并调节肠道微生物群。这项研究为通过静脉内和口服途径抑制乳腺癌及其肺转移的天然外泌体样纳米平台的绿色生产带来了新的见解。
