Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks (MOFs) is important for various biomedical applications, yet remains a challenge. Herein, a simple and general approach to load DNA on the surface of MOFs is developed via one-pot self-assembly of DNA and FeII ions on nanoscale MOFs, resulting in hierarchical core-shell nanostructures of metal-organic@metal-DNA coordination polymers. The strategy enables assembly of DNA molecules on MOFs with ultra-high contents and precise controllability. By incorporation of a chemotherapeutic drug into the Fe-DNA shell, the systems allow to integrate chemotherapy and gene therapy with photodynamic therapy for combinational tumor treatment. Moreover, the hybrid nanostructures enable light-triggered production of cytotoxic singlet oxygen, which further boosts the endosomal escape of the system for an enhanced gene silencing efficacy and thus improved therapeutic outcome. This work highlights a robust approach for the construction of coordination-based drug delivery systems to combat tumor.
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Titanium dioxide nanoparticles (TiO2-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic TiO2-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO2-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO2-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO2-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of Muc2 gene and the absorption of mucin protein by TiO2-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO2-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO2-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population.