PDF(Pubmed)
Abstract：
UNASSIGNED: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.
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.
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.
摘要：
■基于信使RNA(mRNA)的免疫原性疗法作为新兴的肿瘤治疗方法具有重要的前景。然而,现有mRNA方法的递送效率及其在刺激抗肿瘤免疫应答中的有效性需要进一步增强。含有肿瘤特异性抗原和生物标志物的肿瘤细胞裂解物可以触发对肿瘤的更强免疫应答。此外,涉及多种基因治疗的策略为肿瘤基因治疗提供了潜在的优化途径.
■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。
■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。
