Jie Yang,Zengguang Jia,Jun Zhang,Xiuhua Pan,Yawen Wei,Siyu Ma,Ning Yang,Zengyi Liu,Qi Shen
Triple-negative breast cancer (TNBC) patients have a predisposition to poor prognosis due to the strong malignancy. Ferroptosis, a new form of cell death, is a candidate treatment for TNBC owing to its effectiveness in killing cancer cells. However, some TNBC cells exhibit an abnormal tumor metabolism, especially the ferroptosis suppressor protein 1 (FSP1)-mediated ubiquinone redox metabolism, which can promote ferroptosis resistance. Here, rosuvastatin (RSV) is encapsulated in silk fibroin (SF) nanoparticle (designated as Cu-SF(RSV) NPs) for TNBC inhibition by overcoming FSP1-mediated ferroptosis resistance. RSV intervenes in metabolic mevalonate pathway to disturb the redox homeostasis regulated by CoQ/FSP1 axis, thereby overcoming ferroptosis resistance. Besides, Cu-SF(RSV) NPs can generate reactive oxygen species and deplete glutathione to facilitate redox stress, thereby amplifying ferroptosis effect. Thus, it is anticipated that the metabolic intervention nanoparticles, Cu-SF(RSV) NPs, can be exploited as a promising therapeutic platform for clinical TNBC treatment.
As a common complication of spine surgery, postoperative epidural fibrosis is an important cause of failed back surgery syndrome (FBSS), yet there is no effective clinical intervention to tackle it. Herein, for the first time, we develop a strategy of combining a gelatin methacryloyl (GelMA) hydrogel matrix with poly(lactic-co-glycolic acid) (PLGA) microsphere-encapsulated resveratrol (RSV), which aims to synergistically promote the inhibition effect on epidural fibrosis. The resultant RSV@PLGA-GelMA (8% w/v) hydrogels possess optimal mechanical properties and prompt the matrix sustainably and stably to release RSV for several weeks. It is further shown that the hybrid hydrogels without the drug exhibit good biosafety without distinct cytotoxicity, while RSV@PLGA-GelMA could prevent fibroblast proliferation and migration. Further rat laminectomy model indicates that the RSV@PLGA-GelMA hydrogels reduce epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overexpression and deposition via a TGF-β/Smad signaling pathway. Consequently, we believe that such a creative structural combination will be a promising strategy for preventing postoperative epidural fibrosis of spine surgery.
Developing high-performance magnetic particles for the effective separation and purification of target proteins has become an important topic in the area of biomedical research. In this work, a simple and novel strategy was proposed for fabricating magnetic Fe3O4@agarose-iminodiacetic acid-Ni microspheres (MAIN), which can efficiently and selectively isolate histidine-tagged/rich proteins (His-proteins). Based on the thermoreversible sol-gel transition of agarose , basic magnetic agarose microspheres were prepared through the inverse emulsion method, in which the emulsion contained agarose and amine-modified Fe 3 O 4 nanoparticles. The size of the emulsion was controlled by the emulsification of a high-speed shear machine, which improved the specific surface area of MAIN. Subsequently, the amine-modified Fe 3 O 4 nanoparticles were covalently crosslinked with agarose through epichlorohydrin, which could avoid leakage of the magnetic source during use and increase the stability of MAIN. The microsized MAIN exhibited a clearly visible spherical core-shell structure with a diameter range from 3.4 μm to 9.8 μm, and excellent suspension ability in aqueous solution. The maximum adsorption capacity of MAIN for histidine-rich bovine hemoglobin was 1069.2 mg g −1 at 35 °C, which was higher than those of commercialized and most reported magnetic agarose microspheres/nanoparticles. The MAIN showed excellent adsorption ability and selectivity toward His-proteins in a mixture of histidine-rich bovine serum albumin (BSA) and histidine-poor lysozyme (LYZ). When the amount of LYZ was 5-fold higher than that of BSA, the recovery of BSA reached 75.0%. To prove its practicability, MAIN was successfully employed for the enrichment of histidine-tagged RSV-F0 from the cell culture medium supernatant. According to the optimized conditions, MAIN could enrich approximately 0.1 mg of RSV-F0 from 1 mL of complex biological sample. Therefore, we believe that the novel MAIN could be applicable for efficient separation and purification of His-proteins from complex biological systems.
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