UNASSIGNED: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.
UNASSIGNED: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.
UNASSIGNED: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.
■基于先前开发的称为DOTAP-mPEG-PCL(DMP)的理想mRNA递送系统,通过1.2-二油酰基-3-三甲基铵-丙烷(DOTAP)和甲氧基聚(乙二醇)-b-聚(ε-己内酯)(mPEG-PCL)的自组装形成,我们将融合细胞穿透肽(fCPP)引入框架中,并封装肿瘤细胞裂解物以形成新型纳米载体,称为CLSV系统(CLS:CT26肿瘤细胞裂解物,V:纳米载体)。该系统具有促进两种mRNA的递送和通过肿瘤细胞裂解物增强肿瘤免疫原性治疗的双重目的。
合成的CLSV体系的平均尺寸为241.17nm,电位为39.53mV。CLSV系统不仅可以封装肿瘤细胞裂解物,同时将两种mRNA传递给肿瘤细胞,转染效率高达60%。CLSV系统有效激活免疫系统如树突状细胞成熟和激活,导致抗肿瘤免疫反应。通过加载Bim编码的mRNA和IL-23A编码的mRNA,形成CLSV/Bim和CLSV/IL-23A复合物,分别,进一步诱导细胞凋亡和抗肿瘤免疫。制备的CLSV/双mRNA复合物在多种CT26小鼠模型中显示出显著的抗癌作用。
■我们的结果表明,制备的CLSV系统是双mRNA免疫源治疗的理想递送系统。