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.

Although tea polyphenols possess a variety of biological activities, the oxidative stability of tea polyphenols limits its application in the diet as preventive medicine. To enlarge biological activity of tea polyphenols, we investigated changes of tea polyphenols with different pH (3, 4, 5, 6, and 7) at different temperatures (4, 25, and 100°C). Changes in transmittance, deterioration, color values, and contents of catechins were evaluated. The results showed that tea polyphenols with a pH of 3–6 remained stable at 4 and 25°C. With increase of temperature, the tea polyphenol solutions became darker and less green, but deeper yellow in color. When the heating temperature was 100°C, a significant reduction in both total catechins and transmittance was observed. Individual catechins undergo epimerization in this process. Not only temperature and pH, but also heating time influenced the epimerization. Total contents of catechins incubated in pH 3, 4, 5, 6, and 7 citrate buffer solutions for 24 h declined by 15, 24, 41, 57, and 96% at 100°C, respectively. Therefore, tea polyphenols were pH-sensitive: the lower the pH, the more stable the tea polyphenols during storage. Storing at low temperature and acidic pH conditions did not significantly affect the characteristics of tea polyphenols.