Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 790-784, Republic of Korea; Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
School of Integrative Engineering, Chung-Ang University, Seoul 156-75l, Republic of Korea.
J Control Release. 2015 May 10;205:172-80. doi: 10.1016/j.jconrel.2015.01.020. Epub 2015 Jan 21.
CPIEDRPMC (RPM) peptide is a peptide that specifically targets invasive colorectal cancer, which is one of the leading causes of cancer-related deaths worldwide. In this study, we exploited RPM peptide as a targeting ligand to produce a novel and efficient gene delivery system that could potentially be used to treat invasive colon cancer. In order to achieve enhanced specificity to colon cancer cells, the RPM peptide was conjugated to a bioreducible gene carrier consisting of a reducible moiety of disulfide-crosslinked low molecular weight polyethylenimine, IR820 dye, and polyethylene glycol. Here, we examined the physiochemical properties, cytotoxicity, in vitro transfection efficiency, and in vivo biodistribution of the RPM-conjugated polyplex. Our results showed that the RPM-conjugated gene carrier formed a compact polyplex with pDNA that had low toxicity. Furthermore, the RPM-conjugated polymer not only had higher cellular uptake in invasive colon cancer than the non-targeted polymer, but also showed enhanced transfection efficiency in invasive colon cancer cells in vitro and in vivo.
CPIEDRPMC（RPM）肽是一种专门针对侵袭性结直肠癌的肽，侵袭性结直肠癌是全球癌症相关死亡的主要原因之一。在这项研究中，我们利用 RPM 肽作为靶向配体，开发了一种新型有效的基因传递系统，该系统可能用于治疗侵袭性结肠癌。为了提高对结肠癌细胞的特异性，将 RPM 肽与由二硫键交联的低分子量聚乙烯亚胺、IR820 染料和聚乙二醇组成的可还原基因载体偶联。在这里，我们研究了 RPM 缀合的超分子聚合物的物理化学性质、细胞毒性、体外转染效率和体内生物分布。结果表明，RPM 偶联的基因载体与 pDNA 形成了一种具有低毒性的紧凑超分子聚合物。此外，与非靶向聚合物相比，RPM 修饰的聚合物不仅在侵袭性结肠癌细胞中具有更高的细胞摄取率，而且在体外和体内也显示出增强的转染效率。
