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Beyond traditional endothelium-dependent vessel (EDV), vascular mimicry (VM) is another critical tumor angiogenesis that further forms in many malignant metastatic tumors. However, the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors, but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM. Here, we demonstrate a self-assembled nanoparticle (VE-DDP-Pro) featuring self-anti-EDV and -VM capacity enables to significantly enhance the treatment efficacy of cisplatin (DDP) against the growth and metastasis of ovarian cancer. The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles (VE) onto the surface of protamine (Pro) nanoparticle. We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE, which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF, AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT, facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer. Thus, combing with the chemotherapeutics effectiveness of DDP, the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer. We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.

Ovarian cancer (OV) seriously damages women’s health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.

The physically unstable amorphous solid drug can transform into a crystalline state, reducing solubility and dissolution rate. This study aimed to prepare physical stability anticancer drug nilotinib free base amorphous solids by modifying parameters associated with amorphous precipitation, including washing water volume, drying time, and anti-solvent/solvent ratio. Characterization involved powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and data analysis involved pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA) were applied for the physical stability evaluation. The results revealed that amorphous solids showed the highest physical stability under specific conditions: 50 mL washing water volume, 18 h drying time, and 40 anti-solvent/solvent ratio. Hence, it was demonstrated that the method combining PDF analysis and Rcvalues provided a novel and comprehensive assessment of physical stability, offering enhanced speed and accuracy compared to traditional accelerated stability test approaches.

In redox flow electrode capacitive deionization (FCDI), the solubility of the redox electrolyte and flowability of the carbon slurry have a great influence on the salt removal rate and energy consumption. In this work, a mixed solvent electrolyte is proposed for FCDI, which consists of iodide/triiodide redox couples and a carbon slurry in a mixed solvent of water and ethanol (1:1). At a current density of 5 mA cm−2, the salt removal rate in the mixed solvent can reach up to 2.72 μg cm−2s−1, which is much higher than the value of 1.74 μg cm−2s−1and 2.37 μg cm−2s−1obtained in aqueous and ethanol solutions, respectively. This is attributed to the fast transport of ions during the redox reaction in organic solvents and the excellent flowability of the carbon slurry under aqueous conditions, which can provide more reaction sites for iodide/triiodide redox reactions and faster electron transportation. This unique FCDI with organic and aqueous mixed solvent electrolytes provides a new perspective for the development of redox flow electrochemical desalination.

Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2nanoparticles with catalytic activity for active Fenton-like Mn2+delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.