Advanced Materials [IF=27.4]

摘要：The development of prophylactic cancer vaccines typically involves the selection of combinations of tumour-associated antigens, tumour-specific antigens and neoantigens. Here we show that membranes from induced pluripotent stem cells can serve as a tumour-antigen pool, and that a nanoparticle vaccine consisting of self-assembled commercial adjuvants wrapped by such membranes robustly stimulated innate immunity, evaded antigen-specific tolerance and activated B-cell and T-cell responses, which were mediated by epitopes from the abundant number of antigens shared between the membranes of tumour cells and pluripotent stem cells. In mice, the vaccine elicited systemic antitumour memory T-cell and B-cell responses as well as tumour-specific immune responses after a tumour challenge, and inhibited the progression of melanoma, colon cancer, breast cancer and post-operative lung metastases. Harnessing antigens shared by pluripotent stem cell membranes and tumour membranes may facilitate the development of universal cancer vaccines.

摘要：Plant-derived extracellular vesicles(PEVs)have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications. The lipidomic analysis revealed the presence of cytotoxic gingerols and shogaols in ginger-derived EVs(GEVs). Subsequent in vitro and in vivo investigations substantiated the remarkable tumor cell inhibitory and tumor growth suppression efficacy of GEVs. The transcriptomic analysis indicated that GEVs regulate the cell cycle and p53 signaling pathways, thereby inducing cancer cell apoptosis. The supplementary proteomic analysis suggested the potential protein markers in PEV research. These findings highlight the value of multi-omics analyses in elucidating the potential therapeutic effects of PEVs and in advancing the development of PEV-based therapies.

摘要：Diabetic osteoporosis, a prevalent chronic complication of diabetes, is marked by reduced bone mass, increased bone fragility, and susceptibility to fractures. A significant cause of this condition is the disruption of osteoblastic homeostasis due to prolonged hyperglycemia, which impedes bone regeneration and remodeling. Despite its prevalence, no effective treatments specifically target diabetic osteoporosis. Recently, small-activating RNA(saRNA)therapy has attracted attention for its targeting capacity, high efficacy, and minimal side effects. However, RNA’s inherent properties, such as structural instability, susceptibility to degradation, and poor penetration, limit its applications. To address these limitations, a gene-activating tetrahedral framework nucleic acid(tFNA)with sirtuin-1(SIRT1)gene activation function is developed, termed Tsa. Tsa exhibits an RNA-protecting effect and can effectively penetrate cell membranes to upregulate SIRT1 gene expression. At the histological level, Tsa treatment alleviates diabetic osteoporosis by increasing bone trabecular density and promoting new bone formation. At the cellular level, it switches macrophage polarization toward the anti-inflammatory M2 phenotype while inhibiting the inflammatory M1 phenotype, creating a favorable bone immune microenvironment for osteoblasts. At the genetic level, Tsa activates SIRT1 expression, which deacetylates Acetyl-p65 to block the NF-κB pathway and restore the osteoimmune environment. Overall, this research demonstrates a nanodrug “Tsa", capable of activating SIRT1 and modulating the bone immune environment, thereby showcasing its immense potential for diabetic osteoporosis treatment.

摘要：Ferroptosis plays an important role in radiotherapy(RT), and the induction of ferroptosis can effectively sensitize radiotherapy. However, the therapeutic efficiency is always affected by ferroptosis resistance, especially SLC7A11(Solute Carrier Family 7 Member 11)-cystine-cysteine-GSH(glutathione)-GPX4(glutathione peroxidase 4)pathway-mediated resistance. In this study, tumor-microenvironment self-activated high-Z element-containing nanoferroptosis inducers, PEGylated Fe–Bi–SS metal–organic frameworks(FBSP MOFs), were developed to sensitize RT. Unexpectedly, ferroptosis-resistant SLC7A11 would be self-adaptively upregulated, leading to self-responsive ferroptosis resistance. Since the conversion from SLC7A11-transported cystine to cysteine is highly glucose-dependent, glucose oxidase(GOx)was incorporated in the MOFs, causing the depletion of NADPH(nicotinamide adenine dinucleotide phosphate)to terminate the conversion from cystine to cysteine, relieving the self-adaptive ferroptosis resistance. Excitingly, the accumulation of cystine would synergistically lead to disulfide stress and trigger disulfidptosis, making a new contribution to enhance therapeutic efficiency. Moreover, the hydrogen peroxide produced during glucose oxidation could also cascade-react with the Fenton reaction, therefore enhancing ferropotosis. Both in vitro and in vivo results suggested that therapeutic efficiency of ferroptosis-mediated radiosensitization could be enhanced benefiting from synergistic disulfidptosis induction, indicating that disulfidptosis might be an efficient strategy to relieve ferroptosis resistance and enhance RT efficiency.