The therapeutic potential of exosomes in immunotherapy.

Exosomes are found in various tissues of the body and carry abundant contents including nucleic acids, proteins, and metabolites, which continuously flow between cells of various tissues and mediate important intercellular communication. In addition, exosomes from different cellular sources possess different physiopathological immunomodulatory effects, which are closely related to the immune regeneration of normal or abnormal organs and tissues. Here, we focus on the mechanistic interactions between exosomes and the human immune system, introduce the immuno-regenerative therapeutic potential of exosomes in common clinical immune-related diseases, such as infectious diseases, autoimmune diseases, and tumors, and reveal the safety and efficacy of exosomes as a novel cell-free immune regenerative therapy.

Exosomes derived from cancer cells relieve inflammatory bowel disease in mice.

Exosome therapy has garnered significant attention due to its natural delivery capabilities, low toxicity, high biocompatibility, and potential for personalised treatment through engineering modifications. Recent studies have highlighted the ability of tumour cell-derived exosomes (TDEs) to interact with immune cells or modify the immune microenvironment to suppress host immune responses, as well as their unique homing ability to parental cells. The core question of this study is whether this immunomodulatory property of TDEs can be utilised for the immunotherapy of inflammatory diseases. In our experiments, we prepared exosomes derived from murine colon cancer cells CT26 (CT26 exo) using ultracentrifugation, characterised them, and conducted proteomic analysis. The therapeutic potential of CT26 exo was evaluated in our dextran sulphate sodium salt (DSS)-induced inflammatory bowel disease (IBD) mouse model. Compared to the control and 293 T exo treatment groups, mice treated with CT26 exo showed a reduction in the disease activity index (DAI) and colon shortening rate, with no noticeable weight loss. Haematoxylin and eosin (H&E) staining of colon paraffin sections revealed reduced inflammatory infiltration and increased epithelial goblet cells in the colons of CT26 exo-treated group. Furthermore, we conducted preliminary mechanistic explorations by examining the phenotyping and function of CD4+ T cells and dendritic cells (DCs) in the colonic lamina propria of mice. The results indicated that the ameliorative effect of CT26 exosomes might be due to their inhibition of pro-inflammatory cytokine secretion by colonic DCs and selective suppression of Th17 cell differentiation in the colon. Additionally, CT26 exo exhibited good biosafety. Our findings propose a novel exosome-based therapeutic approach for IBD and suggest the potential application of TDEs in the treatment of inflammatory diseases.

Small extracellular vesicles purification and scale-up.

Exosomes are small extracellular vesicles (sEVs) secreted by cells. With advances in the study of sEVs, they have shown great potential in the diagnosis and treatment of disease. However, sEV therapy usually requires a certain dose and purity of sEVs to achieve the therapeutic effect, but the existing sEV purification technology exists in the form of low yield, low purity, time-consuming, complex operation and many other problems, which greatly limits the application of sEVs. Therefore, how to obtain high-purity and high-quality sEVs quickly and efficiently, and make them realize large-scale production is a major problem in current sEV research. This paper discusses how to improve the purity and yield of sEVs from the whole production process of sEVs, including the upstream cell line selection and cell culture process, to the downstream isolation and purification, quality testing and the final storage technology.

[Synthesis and anti-tumor activity of ursolic acid derivatives].

Structure of natural product-ursolic acid was modified for increasing its antitumor activity. Ursolic acid was acylated, esterified, hydrolized or oxidized to obtain target pentacyclic triterpenoid compounds with different substitutes. Sixteen derivatives of ursolic acid were designed and synthesized including eleven new compounds. Anti-tumor activities of ursolic acid and these derivatives against HeLa, SKOV3 and BGC-823 cells in vitro were investigated by MTT assay. The results indicated that compounds 7a and 8a were found to have stronger cell growth inhibitory than ursolic acid on HeLa cells and SKOV3 cells separately, and are worth to be intensively studied further.

Thermodynamic analysis of the effect of the hierarchical architecture of a superhydrophobic surface on a condensed drop state.

Condensed drops usually display a Wenzel state on a superhydrophobic surface (SHS) only with microrough architecture, while Cassie drops easily appear on a surface with micro-nano hierarchical roughness. The mechanism of this is not very clear. It is important to understand how the hierarchical structure affects the states of condensation drops so that a good SHS can be designed to achieve the highly efficient dropwise condensation. In this study, the interface free energy (IFE) of a local condensate, which comes from the growth and combination of numerous initial condensation nuclei, was calculated during its shape changes from the early flat shape to a Wenzel or Cassie state. The final state of a condensed drop was determined by whether the IFE continuously decreased or a minimum value existed. The calculation results indicate that the condensation drops on the surface only with microroughness display a Wenzel state because the IFE curve of a condensed drop first decreases and then increases, existing at a minimum value corresponding to a Wenzel drop. On a surface with proper hierarchical roughness, however, the interface energy curve of a condensed drop will continuously decline until reaching a Cassie state. Therefore, a condensed drop on a hierarchical roughness surface can spontaneously change into a Cassie state. Besides, the states and apparent contact angles of condensed drops on a SHS with different structural parameters published in the literature were calculated and compared with experimental observations. The results show that the calculated condensed drop states are well-coordinated with experimental clarifications. We can conclude that micro-nano hierarchical roughness is the key structural factor for sustaining condensed drops in a Cassie state on a SHS.