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.
Cobalt-incorporated MCM-41(Co-MCM-41) was used as a heterogeneous catalyst for the ozonation of para-chlorobenzoic acid (p-CBA) in aqueous solution. Cobalt oxide supported on MCM-41(Co/MCM-41) was synthesized for comparison. Their textural properties were elucidated by various characterization techniques to understand the relationship between surface texture and catalytic activity. TOC removal at 60 min reached 91% with Co-MCM-41, 83% with Co/MCM-41 and only 52% with ozone alone, respectively. Observations from diffuse reflection spectroscopy demonstrated that different metal phases were formed in these cobalt-modified molecular sieves samples. Radical scavenger experiments indicated the formation of hydroxyl radicals that were responsible for the effective degradation of p-CBA. An integrated approach to the catalytic mechanism was proposed by considering the variation of pH in the course of ozonation as well as its subsequent influence on the dissociation of targeted compounds and surface charge of the catalyst. In the reusability experiments, the reused Co-MCM-41 was able to regain the same catalytic capability as the fresh one within 5 cycles. X-ray photoelectron spectroscopy results indicated that a part of Co2+ was oxidized to Co3+ after oxidation reaction. 相似文献