Surfactant like peptides for targeted gene delivery to cancer cells.
Surfactant like peptides for targeted gene delivery to cancer cells.
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DOI：
10.1016/j.bbrc.2023.02.026
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发表时间：
2023-02
影响因子：
3.1
通讯作者：
Roja Hadianamrei;Mhd Anas Tomeh;Jiqian Wang;Stephen Brown;Xiubo Zhao
中科院分区：
文献类型：
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作者：
Roja Hadianamrei;Mhd Anas Tomeh;Jiqian Wang;Stephen Brown;Xiubo Zhao
表面活性素样多肽(SLP)是一类广泛应用于药物释放和组织工程的两亲性多肽。然而，关于它们在基因传递中的应用的报道很少。本研究旨在开发两种新的SLP，命名为(IA)4K和(IG)4K，用于选择性地将反义寡核苷酸(ODN)和小干扰RNA(SiRNA)输送到癌细胞。采用Fmoc固相合成法合成多肽。用凝胶电泳法和差示扫描量热法研究了它们与核酸的络合作用。在高含量显微镜下检测这些多肽在HCT 116结直肠癌细胞和人真皮成纤维细胞(HDFS)中的转染率。用标准的四甲基偶氮唑盐比色法测定其细胞毒性。用圆二色谱研究了这些多肽与模型膜的相互作用。两种SLP均能高效地将siRNA和ODN导入HCT 116结肠癌细胞，其转染率与商品化的脂类转染剂相当，但对HCT 116的选择性高于HDFS。此外，即使在高浓度和长时间作用下，这两种多肽也表现出很低的细胞毒性。本研究对核酸络合和递送所需的SLP的结构特征提供了更多的见解，因此可以作为合理设计新的SLP的指南，以选择性地将基因输送到癌细胞，以最大限度地减少对健康组织的不良影响。
Surfactant like peptides (SLPs) are a class of amphiphilic peptides widely used for drug delivery and tissue engineering. However, there are very few reports on their application for gene delivery. The current study was aimed at development of two new SLPs, named (IA)4K and (IG)4K, for selective delivery of antisense oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) to cancer cells. The peptides were synthesized by Fmoc solid phase synthesis. Their complexation with nucleic acids was studied by gel electrophoresis and DLS. The transfection efficiency of the peptides was assessed in HCT 116 colorectal cancer cells and human dermal fibroblasts (HDFs) using high content microscopy. The cytotoxicity of the peptides was assessed by standard MTT test. The interaction of the peptides with model membranes was studied using CD spectroscopy. Both SLPs delivered siRNA and ODNs to HCT 116 colorectal cancer cells with high transfection efficiency which was comparable to the commercial lipid-based transfection reagents, but with higher selectivity for HCT 116 compared to HDFs. Moreover, both peptides exhibited very low cytotoxicity even at high concentrations and long exposure time. The current study provides more insights into the structural features of SLPs required for nucleic acid complexation and delivery and can therefore serve as a guide for the rational design of new SLPs for selective gene delivery to cancer cells to minimize the adverse effects in healthy tissues.