Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Pharm Res. 2022 Feb;39(2):353-367. doi: 10.1007/s11095-022-03169-2. Epub 2022 Feb 15.
The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine.
For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells.
The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models.
These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.
新的免疫治疗方法的发明和应用可以弥补传统癌症治疗方法的效率低下，部分原因是肿瘤的抑制性微环境。在这项研究中，我们试图通过沉默肿瘤微环境中的β-连环蛋白的表达并传递白细胞介素（IL）-15 细胞因子来抑制癌细胞的生长并诱导抗肿瘤免疫反应，为树突状细胞（DC）疫苗提供最佳条件。
为此，我们使用叶酸（FA）-修饰的超顺磁性氧化铁纳米粒子（SPION）-羧甲基葡聚糖（CMD）壳聚糖（C）纳米粒子（NPs）来递送抗β-连环蛋白 siRNA 和 IL-15 至癌细胞。
结果表明，β-连环蛋白 siRNA 和 IL-15 的共递送显著降低了癌细胞的生长并增强了免疫反应。该治疗还极大地刺激了 DC 疫苗在触发抗肿瘤免疫中的性能，这在两种不同的癌症模型中抑制了肿瘤的发展并提高了小鼠的存活率。
这些发现表明，使用新型纳米载体（如 SPION-C-CMD-FA）可以作为一种有效的方法，将β-连环蛋白 siRNA、IL-15 和 DC 疫苗的新型联合治疗用于癌症治疗。
