将 mRNA 与 PBS 和钙离子结合可提高 mRNA 转染至肿瘤的效率。
Combining mRNA with PBS and calcium ions improves the efficiency of the transfection of mRNA into tumors.
发表日期:2024 Sep 10
作者:
Noriko Ohta, Takashi Matsuzaki, Masayoshi Nakai, Yasuhiko Tabata, Keisuke Nimura
来源:
Molecular Therapy-Nucleic Acids
摘要:
mRNA 是一种很有前途的体内表达蛋白质的方式。将 mRNA 有效转染到细胞中需要药物递送系统。在这项研究中,我们评估了几种将 mRNA 转染到肿瘤中的药物递送系统。脂质纳米颗粒甚至可以通过瘤内注射将 mRNA 递送至引流淋巴结和肝脏。基于脂质体的系统不能始终如一地为不同类型的肿瘤细胞提供 mRNA。我们发现 PBS 将 mRNA 引入多个肿瘤中,钙离子提高了效率,特别是在雄性小鼠中。圆二色光谱仪表明 PBS 中 mRNA 的结构发生变化。透射电子显微镜显示钙离子促进 PBS 中 mRNA 纳米颗粒的形成。通过 PBS 钙离子转染编码 OX40-配体、白细胞介素 (IL)-36γ 和 IL-23 的 mRNA 可减弱肿瘤生长。我们的结果表明,PBS 与钙离子结合可促进 mRNA 转染至肿瘤中。这些数据为开发用于癌症治疗的 mRNA 转染方法提供了信息。© 2024 作者。
mRNA is a promising modality for expressing a protein in vivo. Drug delivery systems are required for the efficient transfection of mRNA into cells. In this study, we evaluated several drug delivery systems for transfecting mRNA into tumors. A lipid nanoparticle delivered mRNA to the draining lymph nodes and liver, even by intratumoral injection. A liposome-based system did not consistently provide mRNA for different types of tumor cells. We found that PBS introduced mRNA into several tumors, and calcium ions enhanced the efficiency, particularly in male mice. The circular dichroism spectrometer suggested a structural change in mRNA in PBS. Transmission electron microscopy revealed that calcium ions promoted the formation of mRNA nanoparticles in PBS. Transfection of mRNAs coding OX40-ligand, interleukin (IL)-36γ, and IL-23 by PBS + calcium ions attenuated tumor growth. Our results indicate that combining PBS with calcium ions promotes the transfection of mRNA into tumors. These data provide information for the development of methods for transfection of mRNA for cancer therapy.© 2024 The Author(s).