SOX9 Regulates Cancer Stem-Like Properties and Metastatic Potential of Single-Walled Carbon Nanotube-Exposed Cells

Engineered nanomaterials hold great promise for the future development of innovative products but their adverse health effects are a major concern. Recent studies have indicated that certain nanomaterials, including carbon nanotubes (CNTs), may be carcinogenic. However, the underlying mechanisms behind their potential malignant properties remain unclear. In this study, we linked SOX9, a stem cell associated transcription factor, to the neoplastic-like properties of human lung epithelial cells chronically exposed to a low-dose of single-walled carbon nanotubes (SWCNTs). We found that SOX9 is upregulated in SWCNT-exposed cells, which is consistent with their abilities to induce tumor formation and metastasis in vivo. We therefore hypothesized that SOX9 overexpression may be responsible for the neoplastic-like phenotype observed in our model. Indeed, SOX9 knockdown inhibited anchorage-independent cell growth in vitro and lung colonization in vivo in a mouse xenograft model. SOX9 depletion also suppressed the formation of cancer stem-like cells (CSCs), as determined by tumor sphere formation and aldehyde dehydrogenase (ALDH) activity (Aldefluor) assays. Furthermore, SOX9 knockdown suppressed tumor metastasis and the expression of the stem cell marker ALDH1A1. Taken together, our findings provide a mechanistic insight into SWCNT-induced carcinogenesis and the role of SOX9 in CSC regulation and metastasis

Charge Separation/Recombination, Intersystem Crossing, and Unusually Slow Intramolecular Triplet–Triplet Energy Transfer in Naphthalenediimide–Anthracene Compact Energy Donor–Acceptor Dyads

Three anthracene (An)-naphthalenediimide (NDI) compact electron donor-acceptor dyads were prepared. Femtosecond transient absorption (fs-TA) spectra show fast charge separation (ca. 0.9-1.7 ps) and relatively slow charge recombination (ca. 8-565 ps) upon photoexcitation; moreover, the (3)An state was observed for 9-An-NDI, whereas the final state is (NDI)-N-3 for both 9-An-Ph-NDI and 2-An-Ph-NDI, which have an intervening phenyl linker between the An and NDI units. Nanosecond transient absorption (ns-TA) spectra indicate that the lowest triplet state of all the dyads is (3)An, with triplet lifetimes of 139-354 mu s. An unusually slow intramolecular triplet-triplet energy transfer (TTET) was observed for 9-An-Ph-NDI and 2-An-Ph-NDI (32-85 ns). Time-resolved electron paramagnetic resonance (TREPR) spectroscopy confirms that the intersystem crossing (ISC) mechanism is spin orbit charge transfer ISC (SOCT-ISC) for all the dyads; for 9-An-NDI, only the (3)An state was observed, while for the other two dyads, both (NDI)-N-3 and (3)An states were observed, with their relative population changing with increasing delay time, which supports TTET