Polypeptide-engineered DNA tetrahedrons for targeting treatment of colorectal cancer via apoptosis and autophagy
【作者】Zhang, Nan; Yang, Yanan; Wang, Ziyi; Yang, Jing; Chu, Xiao; Liu, Jin; Zhao, Yongxing
【期刊名】Journal of controlled release
【影响因子】 2019年:7.901
【作者单位】Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, PR China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, HeNan Province, Zhengzhou 450001, Henan, PR China; Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, HeNan, Zhengzhou 450001, Henan, PR China.
【年，卷(期)：页码】2019, 309(22): 48-58
【关键词】Anti-cancer peptides; Cell apoptosis; Cell autophagy; Colorectal cancer; DNA tetrahedron
【摘要】Smart delivery of therapeutic peptides that target cellular signaling pathways holds high specificity and great promise for cancer therapy. Here, DNA tetrahedrons (TDs) are designed to carry two therapeutic peptides-FAS peptide and FK-16 peptide. DNA TDs are designed with varied numbers and spatial placement of FAS peptides and FK-16 peptides, and tested for their anti-cancer efficacy. Trimerization of FAS receptors using TDs that are assembled with three FAS peptides enhances FAS-induced cell apoptosis. FK-16 peptides are conjugated to TDs via a peptide sequence sensitive to MMP-2/9 in tumor microenvironment. Therefore, FK-16 peptides are expected to detach from TDs once arrived the tumor microenvironment. A cell penetrating peptide (TAT) is also conjugated to the FK-16 peptide to facilitate its intracellular delivery, which increases the FK-16 peptide-induced cell apoptosis and autophagy. TD-3(TFM)3(FAS) (TFM: TAT + FK-16 + MMP-2/9) exhibits the highest HT-29 inhibition in vitro and in vivo among all therapies. In addition to the high anti-cancer efficacy, TD-3(TFM)3(FAS) shows a high specificity to HT-29 cells in vitro and in vivo. Low cell inhibition rates and cellular uptake are observed in normal cells. In sum, the multifunctional TD-3(TFM)3(FAS) provides a new platform for the smart delivery of anti-cancer peptides to achieve enhanced efficacy and high specificity.
【全文链接】https://www.sciencedirect.com/science/article/pii/S0168365919303992?via%3Dihub
