Title : Iron containing nanoparticles in ultrafast diagnostics and anti-cancer strategies through modulation of tumor microenvironment and ferroptotic cell death
Abstract:
Iron nanoparticles presented superparamagnetic properties and have been widely applied in magnetic force trapping of cells and molecules to accelerate and ease sample preparation. In addition, iron oxide nanoparticles can be designed to convert near infrared (NIR) light to heat thus allowing pyrolysis of samples to obtain genetic materials and to inactivate PCR inhibitors. We utilize such NIR to heat conversion to develop a photothermal qPCR and demonstrated their efficient detection of pathogens in CDI. In addition, Zero valent iron nanoparticles with carboxymethylcellulose shell (ZVI@CMC ) showed prominent anti-cancer activity in various cancer types including oral cancer, colorectal cancer, and non-small cell lung cancers while spare the non-malignant cells. ZVI@CMC induced massive intracellular ROS with accumulation of lipid peroxidation, leading to ferroptotic cell death. Immunoblotting and RT qPCR showed that anti ferroptosis protein, the nuclear factor E2 related factor 2 (NRF2) and its targeting antioxidant genes was attenuated by ZVI@CMC and demonstrated that β-TrCP, AMPK, GSK3β, and mTOR were involved in the axis. Moreover, the IC50 dose of ZVI@CMC was able to inhibit angiogenesis and direct macrophages polarization toward antitumor M1 phenotype. Such dose also significantly increased CD8+ T cells and decreased Treg population. Notably, ZVI@CMC inhibited allograft growth of mouse Lewis lung carcinoma and xenograft growth of human lung carcinoma in mice with reconstituted human immune system. In conclusions, this study identified a novel mechanism that ZVI@CMC enhanced inhibition of NRF2 signaling axis leading to ferroptotic cell death in cancer cells while direct tumor microenvironment toward anti-cancer phenotype including modulation of macrophage polarization, reversal of T cells subpopulation, and inhibition of angiogenesis.
