Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

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.

Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by in vivo RNAi targeting Cyp2e1

Alcoholic liver disease(ALD)results from continuous and heavy alcohol consumption.The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention,which is a long process with poor efficacy and low patient compliance.Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD,but CYP2E1 knockdown in humans was impractical,and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown.In this study,we developed a RNAi therapeutics delivered by lipid nanoparticle,and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks.This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers,and contributed to improved ALD symptoms in mice.The liver fat accumulation,hepatocyte inflammation,and fibrosis were reduced in ALD models.Therefore,this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.

Tuning C-C sp2/sp3 ratio of DLC films in FCVA system for biomedical application

Diamond like carbon(DLC)films with different C-C sp2/sp3 ratios were prepared by tuning the N2 flow rate in a filtered cathodic vacuum arc(FCVA)system.The increase of N2 flow rate facilitated the increase of C-C sp2/sp3 ratio(1.09-2.66),the growth of particle size(0.78-1.58 nm)and the improvement of surface roughness.The SBF immersion results,as well as WCAs(77.57°~71.71°),hemolysis rate(0.14-1.00%)and cytotoxicity level(0)demonstrated that the as-fabricated DLC film was promising for biomedical application.As a result of surface charge effect,the apatite layers formed in the SBF increased with the increase of C-C sp2/sp3 ratio until 1.74 and then showed a tiny decrease during 1.74-2.66.A raise of hemolysis and cytotoxicity was observed when sp2/sp3 ratio was increased.Moreover,a decrease of friction coefficient of Si surface induced by increasing sp2/sp3 ratio was respectively evidenced in ambient air and SBF lubrication environments.