The blood–brain barrier (BBB) is the main bottleneck to prevent some macromolecular substance entering the cerebral circulation, resulting the failure of chemotherapy in the treatment of glioma. Cancer nanotechnology displays potent applications in glioma therapy owing to their penetration across BBB and accumulation into the tumor core. In this study, we have tailored the particle size of mesoporous silica nanoparticles (MSNs) through controlling the hydrolysis rate and polycondensation degree of reactants, and optimized the nanosystem that could effectively penetrate BBB and target the tumor tissue to achieve enhanced antiglioma efficacy. The nanoparticle was conjugated with cRGD peptide to enhance its cancer targeting effect, and then used to load antineoplastic doxorubicin. Therefore, the functionalized nanosystem (DOX@MSNs) selectively recognizes and binds to the U87 cells with higher expression level of ανβ3 integrin, sequentially enhancing the cellular uptake and inhibition to giloma cells, especially the particle size at 40 nm. This particle could rapidly enter cancer cells and was difficult to excrete outside the cells, thus leading to high drug accumulation. Furthermore, DOX@MSNs exhibited much higher selectivity and anticancer activity than free DOX and induced the glioma cells apoptosis through triggering ROS overproduction. Interestingly, DOX@MSNs at about 40 nm exhibited stronger permeability across the BBB, and could disrupt the VM-capability of glioma cells by regulating the expression of E-cadherin, FAK, and MMP-2, thus achieving satisfactory antiglioblastoma efficacy and avoiding the unwanted toxic side effects to normal brain tissue. Taken together, these results suggest that tailoring the particle size of MSNs nanosystem could be an effective strategy to antagonize glioblastoma and overcome BBB.
Exploiting efficient tyrosinase inhibitors and utilizing the inhibition mechanism are of great significance to avoid enzymatic browning in food and skin melanogenesis. Polydatin had excellent tyrosinase inhibitory activity in vitro with IC 50 value of 24.90 μM; however, it exhibited unsatisfactory inhibitory activity intracellularly, which was associated with poor cellular uptake. Fortunately, 6″- O -lauryl polydatin was green-efficiently synthesized by lipase-catalyzed acylation under microwave irradiation. 6″- O -lauryl polydatin exhibited superior mono-/diphenolase inhibitory activity within 100 μM than kojic acid, which had IC 50 of 221 μM. Neither polydatin nor 6″- O -lauryl polydatin bound to the catalytic site, but rather bound noncovalently to the allosteric site 2 of tyrosinase through hydrogen bonds and hydrophobic interactions according to molecular simulations, thereby inducing secondary structure unfolding and reducing tyrosinase activity. 6″- O -lauryl polydatin showed stronger anti-browning effects than polydatin in the natural storage of potato and apple pieces. Polydatin and kojic acid did not induce apoptosis, but 6″- O -lauryl polydatin inhibited human melanin A375 cell proliferation by stimulating ROS overproduction and regulating cell cycle and apoptotic pathways. In addition, lipophilic 6″- O -lauryl polydatin had greater cellular uptake though suffered from intracellular hydrolysis, and exerted better tyrosinase and melanogenesis inhibitory activity than polydatin and kojic acid based on mouse B16F10 melanoma cell model. The results suggested polydatin and 6″- O -lauryl polydatin were promising tyrosinase inhibitors for anti-browning in foods or cosmetics fields.
Blackberry fruit contains high levels of polyphenols particularly anthocyanins which contribute to its biological activities. Bioavailability of polyphenols especially anthocyanins is generally low, it has been proposed that metabolites from polyphenol biotransformation under colonic fermentation are components that exert health benefits. In this study, blackberry was subjected to simulated gastrointestinal digestion and gut microbiota fermentation at different time intervals (0–48 h) to study the changes in bioactive components, its antioxidant and antidiabetic activities. Phenolic compounds, during digestion and fermentation were also analysed. Gut metabolites of blackberry significantly increased the glucose consumption and glycogen content in HepG2 cells. Furthermore, gut metabolites ameliorated high glucose plus palmitic acid-induced ROS overproduction, mitochondrial membrane collapse, and glutathione depletion in HepG2 cells. The mechanism of antidiabetic activity of blackberry was via its potent antioxidant activity. Therefore, our results suggest that blackberry could be recommended as a functional food due to potential antioxidant and antidiabetic activity.
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