Improving the properties of whey protein isolate-zein nanogels with novel acidifiers: Re-dispersity, stability and quercetin bioavailability.

Low bioavailability of quercetin (Que) reduces its preclinical and clinical benefits. In order to improve Que bioavailability, a novel whey protein isolate (WPI)-zein nanogel was prepared by pH-driven self-assembly and heat-induced gelatinization. The results showed that hydrochloric acid can be substituted by both acetic acid and citric acid during the pH-driven process. After encapsulation, the bioavailability of Que in nanogels (composed of 70 % WPI) induced by different acidifiers increased to 19.89 % (citric acid), 21.65 % (hydrochloric acid) and 24.34 % (acetic acid), respectively. Comparatively, nanogels induced by acetic acid showed higher stability (pH and storage stability), re-dispersibility (75.62 %), Que bioavailability (24.34 %), and antioxidant capacity (36.78 % for DPPH scavenging rates). s improved performance of nanogels. In mechanism, acetic acid significantly balanced different intermolecular forces by weakening "acid-induced denaturation" effect. Moreover, the faster binding of Que and protein as well as higher protein molecular flexibility and randomness (higher ratio of random coil) was also observed in nanogels induced by acetic acid. All of these changes contributed to improve nanogels performances. Overall, WPI-zein nanogels induced by acetic acid might be a safe, efficiency and stable delivery system to improve the bioavailability of hydrophobic active ingredients.

Tough porous nanocomposite hydrogel for water treatment.

Developing a cost-effective, stable, and recyclable adsorbent with high adsorption capacity and rapid adsorption kinetics is highly demanded for water treatment but has been proven challenging. Herein, we report a one-step strategy to synthesize tough porous nanocomposite hydrogel, by introducing biochar nanoparticles and interconnected pores into a polyacrylamide hydrogel matrix as an exemplary system. The polyacrylamide hydrogel provides the overall mechanical strength to carry loads and facilitate recycling, the biochar provides adsorptive locus for high adsorption capacity, and the interconnected pores expedite solvent transport for rapid adsorption kinetics. Mechanical characterizations manifest that the porous biochar hydrogel possesses a tensile strength of 128 kPa, a stretchability of 5.9, and a toughness of 538 J m-2. Porous structure analysis reveals that the hydrogel contains an increscent specific surface area by 441% and an augmented pore volume by 279% compared to pure polyacrylamide hydrogel. Experiments pertaining to adsorption isotherms and kinetics, with methylene blue as the model adsorbate, indicate enhanced adsorption performances. The tough hydrogel also allows facile recycling and maintains mechanical robustness after five regeneration cycles. Furthermore, biocompatibility is endorsed by cytotoxicity test. The proposed method could open an ample space for designing and synthesizing tough porous nanocomposite hydrogels for water treatment.

Anisotropic stiffness gradient-regulated mechanical guidance drives directional migration of cancer cells.

Interfacial interactions between cancer cells and surrounding microenvironment involve complex mechanotransduction mechanisms that are directly associated with tumor invasion and metastasis. Matrix remodeling triggers heterogeneity of stiffness in tumor microenvironment and thus generates anisotropic stiffness gradient (ASG). The migration of cancer cells mediated by ASG, however, still remains elusive. Based on a multi-layer polymerization method of microstructured hydrogels with surface topology, we develop an in vitro experimental platform for mechanical interactions of cancer cells with ASG matrix microenvironment. We show that mechanical guidance of mesenchymal cells is essentially modulated by ASG, leading to a spontaneous directional migration along the orientation parallel to the maximum stiffness although there is no stiffness gradient in the direction. The ASG-regulated mechanical guidance presents an alternative way of cancer cell directional migration. Further, our findings indicate that the mechanical guidance occurs only in mesenchymal cancer cells, but not in epithelial cancer cells, implying that cell contractility may contribute to ASG-regulated migration of cells. This work is not only helpful for elucidating the role of matrix remodeling in mediating tumor cell invasion and metastasis, but has potential implications for developing specific cancer treatments. STATEMENT OF SIGNIFICANCE: Local extracellular matrix (ECM) stiffening triggers mechanical heterogeneity in tumor microenvironment, which can exert a crucial impact on interfacial interactions between tumor cells and surrounding ECM. The underlying mechanobiological mechanism that tumor cells are modulated by mechanically heterogeneous ECM, however, still remains mysterious to a great extent. Through our established in vitro platform and analysis, we have demonstrated that anisotropic stiffness gradient (ASG) has the ability to elicit directional migration of cells, essentially depending on local stiffness gradients and the corresponding absolute stiffness values. This study is not only crucial for revealing the role of matrix remodeling in regulating tumor invasion and metastasis, but also offers a valuable guidance for developing anti-tumor therapies from the biomechanical perspective.