Involvement of c-Myc in low dose radiation-induced senescence enhanced migration and invasion of unirradiated cancer cells.

Ionizing radiation is known to cause cell apoptosis at high dose range, but little is known about the cellular response to low dose radiation. In this study, we found that conditioned medium harvested from WI-38 lung fibroblasts and H1299 lung adenocarcinoma cells exposed to 0.1Gy to 1Gy could enhance the migration and invasion of unirradiated H1299 cells in both 2D and 3D culturing circumstances. Low dose radiation did not induce apoptosis, but induced senescence in irradiated cells. We next examined the expression of immediately early genes including c-Myc and K-Ras. Although both genes could be up-regulated by low dose radiation, induction of c-Myc was more specific to low dose range (0.5Gy) at transcriptional and translational levels. Knockdown of c-Myc by shRNA could repress the senescence induced by low dose radiation. The conditioned medium of irradiated cells induced migration of unirradiated cells was also repressed by knockdown of c-Myc. The c-Myc inhibitor 10058-F4 could suppress low dose radiation induced cell senescence, and the conditioned medium harvested from irradiated cells pretreated with 10058-F4 also lost the ability to enhance the migration of unirradiated cells. The cytokine array analysis revealed that immunosuppressive monocyte chemoattractant protein-1 increased by low dose radiation could be repressed by 10058-F4. We also showed that 10058-F4 could suppress low dose radiation induced tumor progression in a xenograft tumor model. Taken together, current data suggest that -Myc is involved in low dose radiation induced cell senescence and potent bystander effect to increase the motility of unirradiated cells.

Photo-responsive degradable hollow mesoporous organosilica nanoplatforms for drug delivery.

BACKGROUND: Stimulus-responsive degradable mesoporous organosilica nanoparticles (MONs) have shown great promise as drug carriers via enhancing the efficiency of drug delivery and accelerating the degradation of nanocarriers. However, it remains a great challenge to develop novel light-enabled spatial and temporal degradable MONs with both superior responsiveness for efficient anti-cancer drug delivery and safe exocytosis. RESULTS: We report a novel photo-responsive degradable hollow mesoporous organosilica nanoplatform (HMONs@GOQD). The platform is based on organosilica nanoparticles (HMONs) containing singlet oxygen (1O2)-responsive bridged organoalkoxysilanes and wrapped graphene oxide quantum dots (GOQDs). The unique hollow mesoporous structure of the HMONs guarantees an excellent drug loading and release profile. During light irradiation, 1O2 produced by the GOQDs leads to the degradation of the organosilica nanoparticles, resulting in enhanced local drug release. CONCLUSIONS: We carried out in vitro and in vivo experiments using DOX as a model drug; DOX-HMONs@GOQDs exhibited high biocompatibility, accelerated degradation, and superior therapeutic efficacy during light irradiation, indicating a promising platform for clinical cancer therapy.