Four novel hexakis C60 derivatives with varying functionalities were synthesized, and their photochemical properties and photodynamic disinfection efficiencies were quantitatively evaluated. All these C. derivatives generated O2 more efficiently than commercial multihydroxylated C60 (fullerol), as assessed by furfuryl alcohol consumption and electron paramagnetic resonance analysis. Despite significant agglomeration/aggregation in the aqueous phase to micrometer-sized particles, nanosecond laser flash photolysis showed that the lifetime of triplet state (a key intermediate for energy transfer responsible for (1)O2 production) was comparable to reported values for pristine C. in organic phase. As a result of facile (1)O2 production, the Co derivatives efficiently inactivated Escherichie coli and MS-2 bacteriophage. Cationic aminofullerene hexakis, which likely exerted electrostatic attraction, exhibited exceptionally rapid virus inactivation even compared to commercial nano-TiO2 photocatalyst These unique photodynamic, hydrophilic and cationic properties may be instrumental for the development of next generation photocatalysts for disinfection applications. The high ROS (reactive oxygen species) production activity and associated cytotoxicity are concerns for potential releases of functionalized Ca to the environment, and require careful assessment apart from other forms of C60 (e.g., nC60) that have been widely studied as model nanomaterials but behave differently.
This study evaluates the potential application of tin porphyrin- and C(60) aminofullerene-derivatized silica (SnP/silica and aminoC(60)/silica) as (1)O(2) generating systems for photochemical degradation of organic pollutants. Photosensitized (1)O(2) production with SnP/silica, which was faster than with aminoC(60)/silica, effectively oxidized a variety of pharmaceuticals. Significant degradation of pharmaceuticals in the presence of the 400-nm UV cutoff filter corroborated visible light activation of both photosensitizers. Whereas the efficacy of aminoC(60)/silica for (1)O(2) production drastically decreased under irradiation with λ > 550 nm, Q-band absorption caused negligible loss of the photosensitizing activity of SnP/silica in the long wavelength region. Faster destruction of phenolates by SnP/silica and aminoC(60)/silica under alkaline pH conditions further implicated (1)O(2) involvement in the oxidative degradation. Direct charge transfer mediated by SnP, which was inferred from nanosecond laser flash photolysis, induced significant degradation of neutral phenols under high power light irradiation. Self-sensitized destruction caused gradual activity loss of SnP/silica in reuse tests unlike aminoC(60)/silica. The kinetic comparison of SnP/silica and TiO(2) photocatalyst in real wastewater effluents showed that photosensitized singlet oxygenation of pharmaceuticals was still efficiently achieved in the presence of background organic matters, while significant interference was observed for photocatalyzed oxidation involving non-selective OH radical.
Refined cancer models are needed to bridge the gap between cell-line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. 38 candidate invasion driver genes were identified, 17 of which have been previously implicated in colorectal cancer progression, including TCF7L2, TWIST2, MSH2, DCC and EPHB1/2. Six invasion driver genes that to our knowledge have not been previously described were validated in vitro using cell proliferation, migration and invasion assays, and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology.
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