白介素 12 (IL-12) 在癌症治疗中具有巨大潜力；然而，其临床应用受到剂量限制性毒性的阻碍。将 IL-12 基因直接递送至肿瘤进行组成性 IL-12 表达是增强其有效性同时最小化全身毒性的可能策略。在这项研究中，我们研究了红细胞源性细胞外囊泡 (RBCEV) 作为 Il-12 质粒递送载体的潜力。我们证明 RBCEV 可以装载编码 IL-12 的小环质粒，并递送至 MB49 膀胱癌细胞以表达 IL-12。来自小环的转基因表达显着高于来自亲本质粒的转基因表达。 RBCEV 介导的 IL-12 表达刺激小鼠脾细胞的免疫反应。肿瘤内递送载有IL-12质粒的RBCEV可抑制膀胱癌肿瘤生长、刺激免疫反应并促进免疫细胞浸润。总之，我们的研究证明了 RBCEV 作为一种有效、安全和可重复剂量的 IL-12 核酸药物递送平台的巨大潜力。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Interleukin-12 (IL-12) holds significant potential in cancer therapy; however, its clinical applicability is hindered by dose-limiting toxicity. Delivery of the IL-12 gene directly to tumours for constitutive IL-12 expression is a possible strategy to enhance its effectiveness while minimizing systemic toxicity. In this study, we investigate the potential of red blood cell-derived extracellular vesicles (RBCEVs) as a carrier for Il-12 plasmid delivery. We demonstrate that RBCEVs can be loaded with minicircle plasmid encoding IL-12 and delivered to MB49 bladder cancer cells for IL-12 expression. The expression of transgenes from minicircles was significantly higher than from the parental plasmids. RBCEV-mediated IL-12 expression stimulated immune responses in mouse splenocytes. Intratumoral delivery of Il-12 plasmid-loaded RBCEVs suppressed bladder cancer tumour growth, stimulated immune responses and promoted immune cell infiltration. In conclusion, our study demonstrates the promising potential of RBCEVs as an effective, safe and redosable nucleic acid drug delivery platform for IL-12.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.