Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance (MDR) is potent to achieve effective cancer treatment. Herein, we report a general method to synthesize pH-dissociable calcium carbonate (CaCO3) hollow nanoparticles with amorphous CaCO3 as the template, gallic acid (GA) as the organic ligand, and ferrous ions as the metallic center via a one-pot coordination reaction. The obtained GA–Fe@CaCO3 exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin, yielding drug loaded GA–Fe@CaCO3 nanotherapeutics featured in pH-responsive size shrinkage, drug release, and Fenton catalytic activity. Compared to nonresponsive GA–Fe@silica nanoparticles prepared with silica nanoparticles as the template, such GA–Fe@CaCO3 confers significantly improved intratumoral penetration capacity. Moreover, both types of drug-loaded GA–Fe@CaCO3 nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate (ATP). As a result, it is found that the doxorubicin loaded GA–Fe@CaCO3 exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies. This work highlights the preparation of pH-dissociable CaCO3-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.
Based on a transient temperature distribution of a 45 steel cylinder workpiece during magnetic quenching, which was obtainedby solving the governing equations with nonlinear boundary on the condition of coupling effects of heat-magnetism. Accordingto the 相似文献
Visualization and artificial intelligence (AI) are well-applied approaches to data analysis. On one hand, visualization can facilitate humans in data understanding through intuitive visual representation and interactive exploration. On the other hand, AI is able to learn from data and implement bulky tasks for humans. In complex data analysis scenarios, like epidemic traceability and city planning, humans need to understand large-scale data and make decisions, which requires complementing the strengths of both visualization and AI. Existing studies have introduced AI-assisted visualization as AI4VIS and visualization-assisted AI as VIS4AI. However, how can AI and visualization complement each other and be integrated into data analysis processes are still missing. In this paper, we define three integration levels of visualization and AI. The highest integration level is described as the framework of VIS+AI, which allows AI to learn human intelligence from interactions and communicate with humans through visual interfaces. We also summarize future directions of VIS+AI to inspire related studies. 相似文献
Combining chemotherapy and radiotherapy (chemoradiotherapy) has been widely applied in many clinical practices, showing promises in enhancing therapeutic outcomes. Nontoxic nanocarriers that not only are able to deliver chemotherapeutics into tumors, but could also act as radiosensitizers to enhance radiotherapy would thus be of great interest in the development of chemoradiotherapies. To achieve this aim, herein mesoporous tantalum oxide (mTa2O5) nanoparticles with polyethylene glycol (PEG) modification are fabricated. Those mTa2O5‐PEG nanoparticles could serve as a drug delivery vehicle to allow efficient loading of chemotherapeutics such as doxorubicin (DOX), whose release appears to be pH responsive. Meanwhile, owing to the interaction of Ta with X‐ray, mTa2O5‐PEG nanoparticles could offer an intrinsic radiosensitization effect to increase X‐ray‐induced DNA damages during radiotherapy. As a result, DOX‐loaded mTa2O5‐PEG (mTa2O5‐PEG/DOX) nanoparticles can offer a strong synergistic therapeutic effect during the combined chemoradiotherapy. Furthermore, in chemoradiotherapy, such mTa2O5‐PEG/DOX shows remarkably reduced side effects compared to free DOX, which at the same dose appears to be lethal to animals. This work thus presents a new type of mesoporous nanocarrier particularly useful for the delivery of safe and effective chemoradiotherapy. 相似文献