1 Department of Biochemistry and Biophysics, Stockholm University.
2 Department of Chemistry, Faculty of Science, Assuit University Assuit, Egypt.
J Biomater Appl. 2018 Sep;33(3):392-401. doi: 10.1177/0885328218796623.
Gene-based therapies, including the delivery of oligonucleotides, offer promising methods for the treatment of cancer cells. However, they have various limitations including low efficiency. Herein, cell-penetrating peptides (CPPs)-conjugated chitosan-modified iron oxide magnetic nanoparticles (CPPs-CTS@MNPs) with high biocompatibility as well as high efficiency were tested for the delivery of oligonucleotides such as plasmid pGL3, splice correction oligonucleotides, and small-interfering RNA. A biocompatible nanocomposite, in which CTS@MNPs was incorporated in non-covalent complex with CPPs-oligonucleotide, is developed. Modifying the surface of magnetic nanoparticles with cationic chitosan-modified iron oxide improved the performance of magnetic nanoparticles-CPPs for oligonucleotide delivery. CPPs-CTS@MNPs complexes enhance oligonucleotide transfection compared to CPPs@MNPs or CPPs. The hydrophilic character of CTS@MNPs improves complexation with plasmid pGL3, splice correction oligonucleotides, and small-interfering RNA payload, which consequently resulted in not only strengthening the colloidal stability of the constructed complex but also improving their biocompatibility. Transfection using PF14-splice correction oligonucleotides-CTS@MNPs showed sixfold increase of the transfection compared to splice correction oligonucleotides-PF14 that showed higher transfection than the commercially available lipid-based vector Lipofectamine™ 2000. Nanoscaled CPPs-CTS@MNPs comprise a new family of biomaterials that can circumvent some of the limitations of CPPs or magnetic nanoparticles.
基因治疗，包括寡核苷酸的递呈，为癌细胞的治疗提供了很有前途的方法。然而，它们有各种局限性，包括效率低。在此，测试了细胞穿透肽（CPPs）-壳聚糖修饰的氧化铁磁性纳米粒子（CPPs-CTS@MNPs）作为高效的寡核苷酸递呈载体，如质粒 pGL3、剪接校正寡核苷酸和小干扰 RNA。开发了一种具有生物相容性的纳米复合材料，其中 CTS@MNPs 与 CPPs-寡核苷酸以非共价复合物的形式存在。用阳离子壳聚糖修饰的氧化铁修饰磁性纳米粒子的表面，提高了磁性纳米粒子-CPPs 对寡核苷酸递呈的性能。与 CPPs@MNPs 或 CPPs 相比，CPPs-CTS@MNPs 复合物增强了寡核苷酸转染。CTS@MNPs 的亲水性改善了与质粒 pGL3、剪接校正寡核苷酸和小干扰 RNA 有效负载的复合物形成，这不仅增强了所构建复合物的胶体稳定性，而且提高了其生物相容性。用 PF14-剪接校正寡核苷酸-CTS@MNPs 进行转染，与显示出比商业上可利用的脂质载体 Lipofectamine™ 2000 更高转染率的剪接校正寡核苷酸-PF14 相比，转染效率提高了六倍。纳米级 CPPs-CTS@MNPs 组成了一类新的生物材料，可以规避 CPPs 或磁性纳米粒子的一些局限性。
