Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy.

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.

Micronization Effects on Structural, Functional, and Antioxidant Properties of Wheat Bran.

To explore the effect of micronization on the structural, functional, and antioxidant properties of wheat bran, wheat bran with mean particle size (D50) of 46.08, 34.29, 26.51, 26.35, and 26.05 µm were prepared by using an ultrafine pulverizer under different rolling frequencies (0, 6, 9, 12, and 15 times). The main chemical components and structural, functional, and antioxidant properties of the wheat bran were compared and a correlation analysis was conducted. As the D50 of the wheat bran decreased from 46.08 µm to 26.05 µm, the micromorphology exhibited the destruction of the bundle structure, which is formed by starch and fiber, during which the starch particles peeled off, the fiber fragments destructed, and some of the slim fiber fragments attached to the surfaces of the starch granules. According to the X-ray diffraction pattern, part of the crystalline structure was transformed into an amorphous structure and the crystallization index decreased from 13.08% to 3.95%. According to the near-infrared spectrum, more active groups, such as the hydroxyl group, were exposed; however, no new groups were generated. These structural changes accordingly caused changes in the chemical components, functional properties, and antioxidant properties of the wheat bran. Specifically, the protein, total phenols, total flavonoids, and fatty acid content increased by 6.72%, 23.47%, 19.07%, and 172.88%, respectively. The lipase activity, antioxidant activity in vitro (DPPH• scavenging activity, ABTS+• scavenging activity, and ferric reducing antioxidant power), and the water-holding, cholesterol-adsorption, sodium nitrite-adsorption, and cation-exchange capacities, were enhanced to some extent. The oil-holding capacity decreased from 3.01 g/g to 1.32 g/g. The swelling capacity decreased first and then increased and the swelling capacity of the wheat bran with a D50 of 34.29 µm was the lowest (3.62 mL/g). Therefore, the micronization could be used as a pretreatment method to improve the functional and antioxidant properties of wheat bran; however, the optimal particle size of wheat bran is based on the function of the product.