Metal-polyphenol-network coated CaCO3 as pH-responsive nanocarriers to enable effective intratumoral penetration and reversal of multidrug resistance for augmented cancer treatments

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.

     

Collective reflection strategy for moderating conformity tendency and promoting reflective judgment performance

Reflective judgement is crucial for medical-related practitioners in dealing with controversial issues. However, the conformity phenomenon is likely to occur and interfere with reflective judgement learning during interactive activities. Effective strategies are required to moderate the conformity behaviour tendency (CBT) and improve reflective judgement performance (RJP). This study demonstrates two significant results: (a) Compared with the guided self-reflection learning strategy, the online collective reflection (OCR) learning strategy effectively weakened the learners' general CBT while dealing with professional controversial issues; and (b) a significantly negative correlation between the RJP achieved and the change of CBT in online environment was detected in the OCR group. The implications and potential applications in higher education were discussed. Further studies are needed to confirm the long-term effects and the extending application to other professional studies.     

Photopolymerization synthesis of polyacrylic acid dispersant with methoxysilicon end groups and its application in a nano‐SiO2 aqueous system

In order to improve the dispersity and stability of the nano‐SiO₂ aqueous system with high solid content, a kind of polyacrylic acid dispersant with methoxysilicon end groups (KH590‐PAA) was synthesized by photopolymerization of acrylic acid (AA) initiated with (3‐mercaptopropyl)trimethoxysilane (KH590). After adding KH590‐PAA into the nano‐SiO₂ aqueous dispersion system (20 wt% solid content), the viscosity and the curing time of the system were measured with a rotational viscometer and the inverted bottle method. Moreover, the dispersion mechanism of KH590‐PAA for the nano‐SiO₂ aqueous system was researched by measuring the adsorption capacity, the particle size and the zeta potential of the nanoparticles with a conductivity meter, dynamic light scattering, SEM and TEM, respectively. The results showed that the methoxysilicon groups in KH590‐PAA could react with hydroxyl groups on the surface of nano‐SiO₂ in the process of stirring, which enhanced the adsorption capacity of the dispersant and then increased the surface charge of the particles. Therefore, electrostatic repulsion and steric hindrance effects between the SiO₂ nanoparticles could be further enhanced by adding the KH590‐PAA dispersant, and then the nano‐SiO₂ aqueous system exhibited better dispersity and stability. Besides, the dispersion properties of SiO₂ nanoparticles in water were closely related to the addition amount and the molecular weight of the KH590‐PAA dispersant. © 2018 Society of Chemical Industry     

Triphenylphosphonium (TPP)-Based Antioxidants: A New Perspective on Antioxidant Design

Mitochondrial oxidative damage and dysfunction contribute to a wide range of human diseases. Considering the limitation of conventional antioxidants and that mitochondria are the main source of reactive oxygen species (ROS) which induce oxidative damage, mitochondria-targeted antioxidants which can selectively block mitochondrial oxidative damage and prevent various types of cell death have been widely developed. As a lipophilic cation, triphenylphosphonium (TPP) has been commonly used in designing mitochondria-targeted antioxidants. Conjugated with the TPP moiety, antioxidants can achieve more than 1000-fold higher mitochondrial concentration depending on cell membrane potentials and mitochondrial membrane potentials. Herein we discuss the deficiencies of conventional antioxidants and the advantages of mitochondrial targeting, and review various types of TPP-based mitochondria-targeted antioxidants. These provide theoretical and background support for the design of new anti-oxidant.     

Effect of hyperbranched poly(citric polyethylene glycol) with various polyethylene glycol chain lengths on starch plasticization and retrogradation

A series of hyperbranched poly(citric polyethylene glycol) (PCPEG) materials with varied polyethylene glycol (PEG) chain lengths as plasticizers were mixed with maize starch (MS) via cooking and film‐forming. The structure, pasting property, plasticization, aging property, moisture absorption and compatibility of plasticized starches were studied by means of Fourier transform infrared spectroscopy, X‐ray diffraction, rapid viscosity analysis, tension testing, moisture absorption measurements and scanning electron microscopy. Compared with PEG and citric acid, PCPEG was more effective in promoting starch chain movement and inhibiting the retrogradation of starch film. Also, PCPEG/MS had smaller moisture content. The longer the plasticizer chain, the better were the aging resistance and moisture resistance of starch. But with an increase of PEG chain length, mechanical properties of PCPEG/MS deteriorated and the compatibility between PCPEG and MS decreased. The hyperbranched derivative of PEG with longer chain exhibited improved plasticization and compatibility with starch. © 2019 Society of Chemical Industry