Lee Dian-Jang, Wagner Ernst
Department of Pharmacy, Center for NanoScience, Ludwig-Maximilians-Universität München, Munich, Germany.
Nanosystems Initiative Munich (NIM), Munich, Germany.
Methods Mol Biol. 2019;1974:83-98. doi: 10.1007/978-1-4939-9220-1_7.
As synthetic small interfering RNA (siRNA) against antitumoral gene targets show promise for cancer treatment, different siRNA delivery systems have sparkled intense investigations. To develop tumor-specific carriers for cytosolic and systemic siRNA delivery, our laboratory has recently generated folate-conjugated targeted combinatorial siRNA polyplexes based on sequence-defined oligomer platform compatible with solid-phase-supported synthesis. These polyplexes presented efficient siRNA-mediated gene silencing in folate receptor-expressing tumors in vitro and in vivo. In this chapter, we provide a brief background on the formulation design and detailed protocols to evaluate polyplex formation, gene silencing efficiency, and receptor-directed cell killing in cancer cells using targeted combinatorial siRNA polyplexes.
由于针对抗肿瘤基因靶点的合成小干扰RNA（siRNA）在癌症治疗中显示出前景，不同的siRNA递送系统引发了深入研究。为了开发用于胞质和全身siRNA递送的肿瘤特异性载体，我们实验室最近基于与固相支持合成兼容的序列定义寡聚物平台，生成了叶酸共轭的靶向组合siRNA多聚体。这些多聚体在体外和体内表达叶酸受体的肿瘤中呈现出高效的siRNA介导的基因沉默。在本章中，我们提供了关于制剂设计的简要背景以及详细方案，以评估使用靶向组合siRNA多聚体在癌细胞中形成多聚体、基因沉默效率和受体导向的细胞杀伤作用。
