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Novel core-shell-shell structured nanoparticles 75 nm in diameter with all-in-one "smart" functional capabilities for simultaneous photoresponsive drug release, photodynamic therapy, and cell imaging are designed and prepared. These nanoparticles consist of an upconversion (UC) emission core, a photosensitizer-embodied silica sandwich shell, and a β-cyclodextrin (β-CD) gated mesoporous silica outmost shell with drugs (Rhodamine B as a model) loaded inside. We show in this proof-of-concept demonstration that, under 980 nm near-infrared irradiation, UC 540 nm green light emissions were emitted for cell imaging, and 660 nm red light emissions were excited for activating photosensitizers to generate singlet oxygen, which could be exploited directly to kill cancer cells and simultaneously dissociate β-CD gatekeeper to release drugs. The preliminary results reported here will shed new light on the future design and applications of multifunctional platforms for cancer therapy and diagnostic.

BackgroundMicrobial lipids have drawn increasing attention in recent years as promising raw materials for biodiesel production, and the use of lignocellulosic hydrolysates as carbon sources seems to be a feasible strategy for cost-effective lipid fermentation with oleaginous microorganisms on a large scale. During the hydrolysis of lignocellulosic materials with dilute acid, however, various kinds of inhibitors, especially large amounts of organic acids, will be produced, which substantially decrease the fermentability of lignocellulosic hydrolysates. To overcome the inhibitory effects of organic acids, it is critical to understand their impact on the growth and lipid accumulation of oleaginous microorganisms.ResultsIn our present work, we investigated for the first time the effect of ten representative organic acids in lignocellulosic hydrolysates on the growth and lipid accumulation of oleaginous yeast Trichosporon fermentans cells. In contrast to previous reports, we found that the toxicity of the organic acids to the cells was not directly related to their hydrophobicity. It is worth noting that most organic acids tested were less toxic than aldehydes to the cells, and some could even stimulate the growth and lipid accumulation at a low concentration. Unlike aldehydes, most binary combinations of organic acids exerted no synergistic inhibitory effects on lipid production. The presence of organic acids decelerated the consumption of glucose, whereas it influenced the utilization of xylose in a different and complicated way. In addition, all the organic acids tested, except furoic acid, inhibited the malic activity of T. fermentans. Furthermore, the inhibition of organic acids on cell growth was dependent more on inoculum size, temperature and initial pH than on lipid content.ConclusionsThis work provides some meaningful information about the effect of organic acid in lignocellulosic hydrolysates on the lipid production of oleaginous yeast, which is helpful for optimization of biomass hydrolysis processes, detoxified pretreatment of hydrolysates and lipid production using lignocellulosic materials.

A cascade-reaction enabled synergistic starvation/ROS-mediated/chemo-therapy was developed, and it exhibits a remarkable therapeutic efficacy without any external intervention.

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Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif-containing (TRIM)-28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear. In this study, we investigated the role of TRIM28 in inflammatory responses and angiogenic activity of ECs for the first time. We showed that TRIM28 is the most abundant TRIM family member and is localized in nuclei of ECs. Small interfering RNA-mediated knockdown of TRIM28 strikingly suppressed expression of TNF receptor (TNFR)-1 and -2, decreased TNF-α-induced phosphorylation of IKKα/β and IκBα and degradation of IκBα and nuclear translocation of p65, and suppressed basal level and TNF-α-induced expression of chemokines and adhesion molecules, including VCAM-1, IL-6, ICAM-1, E-selectin, and monocyte chemoattractant protein (MCP)-1. Unexpectedly, IL-8 was potentiated by TRIM28 knockdown in ECs in an NF-κB-inducing kinase-dependent manner. Meanwhile, knockdown of TRIM28 inhibited expression of VEGF receptor 2 and suppressed VEGF-induced proliferation and tube formation by ECs. Finally, knockdown of TRIM28 suppressed recruitment of ECs in a murine synthetic basement membrane model. In summary, we found that TRIM28 acts as a central factor in controlling endothelial inflammatory responses and angiogenic activities by retaining expression of TNFR-1 and -2 and VEGF receptor 2 in ECs.-Wang, Y., Li, J., Huang Y., Dai, X., Liu, Y., Liu, Z., Wang, Y., Wang, N., Zhang, P. Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR1 and -2 and VEGFR2 in endothelial cells.

A novel photodynamic therapy nanoplatform based on mesoporous-silica-coated upconverting nanoparticles (UCNP) with electrostatic-driven ultrafast photosensitizer (PS) loading and 808 nm near infrared (NIR)-light-triggering capabilities has been fabricated. By positively charging inner channels of the mesoporous silica shell with amino groups, a quantitative dosage of negatively charged PS, exemplified with Rose Bengal (RB) molecules, can be loaded in 2 min. In addition, the electrostatic-driven technique simultaneously provides the platform with both excellent PS dispersity and leak-proof properties due to the repulsion between the same-charged molecules and the electrostatic attraction between different-charged PS and silica channel walls, respectively. The as-coated silica shell with an ultrathin thickness of 12±2 nm is delicately fabricated to facilitate ultrafast PS loading and efficient energy transfer from UCNP to PS. The outside surface of the silica shell is capped with hydrophilic β-cyclodextrin, which not only enhances the dispersion of resulting nanoparticles in water but also plays a role of "gatekeeper", blocking the pore opening and preventing PS leaking. The in vitro cellular lethality experiment demonstrates that RB molecules can be activated to effectively generate singlet oxygen and kill cancer cells upon 808 nm NIR light irradiation.

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