Tailored design of NHS-SS-NHS cross-linked chitosan nano-hydrogels for enhanced anti-tumor efficacy by GSH-responsive drug release.

The traditional chemotherapeutic agents' disadvantages such as high toxicity, untargeting and poor water solubility lead to disappointing chemotherapy effects, which restricts its clinical application. In this work, novel size-appropriate and glutathione (GSH)-responsive nano-hydrogels were successfully prepared via the active ester method between chitosan (containing -NH2) and cross-linker (containing NHS). Especially, the cross-linker was elaborately designed to possess a disulfide linkage (SS) as well as two terminal NHS groups, namely NHS-SS-NHS. These functionalities endowed chitosan-based cross-linked scaffolds with capabilities for drug loading and delivery, as well as a GSH-responsive mechanism for drug release. The prepared nano-hydrogels demonstrated excellent performance applicable morphology, excellent drug loading efficiency (∼22.5%), suitable size (∼100 nm) and long-term stability. The prepared nano-hydrogels released over 80% doxorubicin (DOX) after incubation in 10 mM GSH while a minimal DOX release less than 25% was tested in normal physiological buffer (pH = 7.4). The unloaded nano-hydrogels did not show any apparent cytotoxicity to A 549 cells. In contrast, DOX-loaded nano-hydrogels exhibited marked anti-tumor activity against A 549 cells, especially in high GSH environment. Finally, through fluorescent imaging and flow cytometry analysis, fluorescein isothiocyanate-labeled nano-hydrogels show obvious specific binding to the GSH high-expressing A549 cells and nonspecific binding to the GSH low-expressing A549 cells. Therefore, with this cross-linking approach, our present finding suggests that cross-linked chitosan nano-hydrogel drug carrier improves the anti-tumor effect of the A 549 cells and may serve as a potential injectable delivery carrier.

Effects of immersion in a simulated natural environment on stress reduction and emotional arousal: A systematic review and meta-analysis.

Background: Although the mental health benefits of exposure to simulated natural environments are well established by researchers from environmental psychology, landscape architecture, and public health, it is unclear whether and to what extent technological immersion affects these benefits. Methods: Systematical literature searches were conducted in May 2022 from six databases. The risk of bias was evaluated using the Cochrane's Risk of Bias tool 2.0 and the Risk of Bias in Non-randomized Studies of Interventions tool. We performed a random-effects meta-regression to investigate the heterogeneity. The immersion levels of included studies were classified by projection devices and motion capture, and then subgroup analysis was conducted. Results: Twenty-six publications were included. Exposure to simulated nature was confirmed to be associated with increased positive affect 0.40 [95% confidence interval (CI): 0.22, 0.58], vigor 0.58 (95% CI: 0.30, 0.86), calmness 0.54 (95% CI: 0.17, 0.92) and decreased perceived stress -0.38 (95% CI: -0.71, -0.06), total mood disturbance -0.87 (95% CI: -1.17, -0.57), tension -0.70 (95% CI: -0.99, -0.41), fatigue -0.60 (95% CI: -0.91, -0.28), anxiety -0.72 (95% CI: -1.43, -0.02), depression -0.33 (95% CI: -0.52, -0.14), confusion -0.79 (95% CI: -1.19, -0.40), and anger -0.54 (95% CI: -0.76, -0.31). Gender, health status, study design, mean age, and single exposure duration were not significant when entered in a meta-regression. For positive affect, medium immersion was observed to produce a larger effect than low and high immersion. All included studies had a moderate to high risk of bias. Conclusion: Audio-visual exposure to simulated nature contributes to stress relief and emotional arousal. The immersion level explains the heterogeneity of positive affect triggered by simulated nature. Focusing on the technical features will open up new possibilities for combining actual and simulated nature's mental health benefits.