A Nanoplatform Based on Pillar[5]arene Nanovalves for Combined Drug Delivery and Enhanced Antitumor Activity.

Modern nanodrug delivery technologies offer new approaches in the fight against cancer. However, due to the heterogeneity of tumors and side effects of anticancer drugs, monotherapies are less effective. Herein, we report a novel pH and light dual-responsive nanodrug delivery platform. The platform was formed by sulfonate-modified gold nanoparticles loaded with the anticancer drugs doxorubicin (DOX) and glucose oxidase (GOx) and then covered by water-soluble pillar[5]arene as a nanovalve. The nanovalve formed by the host-guest interaction between pillar[5]arene and the sulfonic acid group grafted onto the gold nanoparticle increased the drug loading capacity of the nanoplatform and enabled sustained release of the drug in a simulated weakly acidic tumor environment. The released GOx can consume intracellular glucose, namely, starvation therapy, while the generated hydrogen peroxide can further kill tumor cells, complementing DOX chemotherapy. Gold nanoparticles have good photothermal conversion ability and can enhance the drugs release rate under specific wavelengths of light irradiation. The results of in vitro and in vivo experiments showed that this novel nanodrug delivery platform has good biocompatibility and better therapeutic efficacy relative to monotherapy. This study successfully developed a combined chemo/starvation therapy strategy with good tumor suppression, providing a new approach for cancer treatment.

Preparation and Evaluation of Curcumin Derivatives Nanoemulsion Based on Turmeric Extract and Its Antidepressant Effect.

Purpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect. Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted. Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration. Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.