Glioblastoma (GBM) is the most aggressive brain tumor, which owns the characteristics of high recurrence, low survival rate and poor prognosis because of the existence of blood brain barrier (BBB) and complicated brain tumor microenvironment. Currently, immunotherapy has attracted much attention on account of favorable therapeutic effect. In this study, we designed a cRGD-modified cancer cell membrane (CM) coated calcium carbonate nanoparticle to deliver interleukin-12 messenger RNA (IL-12 mRNA@cRGD-CM-CaCO₃ NPs). The cRGD-modified CM as the shell can endow the nanoparticles with BBB crossing and tumor homing/homotypic targeting effect in the brain tumor microenvironment. IL-12 mRNA-loaded calcium carbonate nanoparticles as the core allow synergistic immunotherapy of necroptosis-induced immune response and IL-12 mRNA transfection under ultrasound irradiation. The as-prepared biomimetic nanoparticles showed superior target and immunotherapeutic outcomes, suggesting that this biomimetic nanoplatform provides a feasible strategy for promoting BBB-penetrating and antitumor immunity.

Atherosclerosis (AS), a chronic arterial disease, is the leading cause of death in western developed countries. Considering its long-term asymptomatic progression and serious complications, the early prevention and effective treatment of AS are particularly important. The unique characteristics of nanoparticles (NPs) make them attractive in novel therapeutic and diagnostic applications, providing new options for the treatment of AS. With the assistance of reactive oxygen species (ROS)-based NPs, drugs can reach specific lesion areas, prolong the therapeutic effect, achieve targeted controlled release and reduce adverse side effects. In this article, we reviewed the mechanism of AS and the generation and removal strategy of ROS. We further discussed ROS-based NPs, and summarized their biomedical applications in scavenger and drug delivery. Furthermore, we highlighted the recent advances, challenges and future perspectives of ROS-based NPs for treating AS.

Introduction: The side effects of conventional therapy for acute deep vein thrombosis (DVT) are severe, with inflammatory reactions playing a pivotal role. It is particularly important to explore new ways of treatment thrombosis by targeting inflammatory factors.Methods: A targeted microbubble contrast agent was prepared using the biotin-avidin method. The 40 DVT model rabbits were established and divided into four groups according to different treatment regimens. The four coagulation indexes, TNF-α, and D-dimer content of experimental animals were measured before modeling and before and after treatment, and the thrombolysis was assessed by ultrasound imaging. Finally, the results were verified by pathology.Results and Discussion: Fluorescence microscopy verified the successful preparation of targeted microbubbles. Among the groups, PT, APTT, and TT in Group II-IV were longer than those in Group I (all p < 0.05). FIB and D-dimer content were lower than those in Group I (all p < 0.05), and TNF-α content in Group IV was lower than that in Group I-III (all p < 0.05). Pairwise comparison before modeling and before treatment and after treatment showed that, after treatment, the PT, APTT, and TT in Group II-IV were longer than those before modeling (all p < 0.05). The contents of FIB and D-dimer were lower than those before modeling and before treatment (all p < 0.05). The content of TNF-α decreased significantly only in Group IV, but increased in the other three groups. Targeted microbubbles combined with Low-power focused ultrasound can reduce inflammation, significantly promote thrombolysis, and provide new ideas and methods for the diagnosis and treatment of acute DVT.

Background. This study investigated whether vascular endothelial necroptosis is involved in deep vein thrombosis (DVT) and how IL-17B facilitates necroptosis signaling. Methods. The DVT mouse model was induced by ligation of the IVC. The cross-sectional area of thrombus increases and the thrombus occupied the entire venous lumen at 48 h after ligation. Meanwhile, the increased expression of p-RIP3/RIP3 was most pronounced at 48 h after ligation, and the p-MLKL/MLKL peaked at 72 h. Results. Based on Illumina sequencing and KEGG pathway analyses, the activated RIP3/MLKL is associated with increased IL-17B. With thrombus formation, IL-17B was upregulated and enhanced the expression of RIP3 and MLKL in the IVC wall, as well as their phosphorylation levels (all , the comparison group consisted of the control group, DVT group, DVT/IL-17B group, and DVT/anti-IL-17B group). The p-RIP3/RIP3 and p-MLKL/MLKL ratios were reduced by anti-IL-17B. Similarly, the weight and cross-sectional area of the thrombi were increased by IL-17B and decreased by the IL-17B antibody. IL-17B had a smaller effect on thrombosis in knockout mice compared with WT mice. In vitro, the IL-17B protein expression and the level of RIP3 and MLKL phosphorylation increased high in the OGD cells, accompanied by increased expression of IL-6 and TNF-α. IL-17B enhanced the expression of IL-6 and TNF-α but had little effect on the IL-6 and TNF-α after transfected with siRIP3 or siMLKL. Similarly, the plasma IL-17B, IL-6, and TNF-α were significantly increased after thrombosis in WT mice, and enhanced by IL-17B. But IL-17B did not increase the plasma IL-6 and TNF-α in knockout mice. Conclusions. In conclusion, those results suggest that vascular endothelial necroptosis plays a crucial role in vascular injury and IL-17B could enhance the necroptosis pathway.