Oligosarcosine Conjugation of Arginine-Rich Peptides Improves the Intracellular Delivery of Peptide/pDNA Complexes

被引:3
|
作者
Yokoo, Hidetomo [1 ,2 ]
Dirisala, Anjaneyulu [1 ]
Uchida, Satoshi [1 ,2 ,3 ]
Oba, Makoto [2 ]
机构
[1] Kawasaki Inst Ind Promot, Innovat Ctr Nanomed, Kawasaki 2100821, Japan
[2] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Med Chem, Kyoto 6060823, Japan
[3] Tokyo Med & Dent Univ TMDU, Med Res Inst, Dept Adv Nanomed Engn, Tokyo 1138510, Japan
基金
日本学术振兴会;
关键词
cell-penetrating peptides; nonproteinogenic amino acids; sarcosine; pDNAdelivery; CELL-PENETRATING PEPTIDES; DNA DELIVERY; COPOLYMERS SYNTHESIS; PEGYLATED POLYPLEX; VECTORS;
D O I
10.1021/acsbiomaterials.3c01542
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Cell-penetrating peptides (CPPs), for example, arginine (Arg) rich peptides, are used for the intracellular delivery of nucleic acids. In this study, oligosarcosine-conjugated Arg-rich peptides were designed as plasmid DNA (pDNA) carriers, and the physicochemical parameters and transfection efficiency of the peptide/pDNA complexes were evaluated. Oligosarcosine with different lengths were conjugated to a base sequence composed of arginine and alpha-aminoisobutyric acid (Aib) [(Aib-Arg-Arg)3]. Oligosarcosine conjugation inhibited the aggregation of the complexes after mixing with pDNA, shielded the positive charge of the complexes, and provided efficient pDNA transfection in cultured cells. The efficiency of the pDNA transfection was improved by varying the length of the oligosarcosine moiety (10-15 units were optimal). The cellular uptake efficiency and intracellular distribution of pDNA were the same regardless of oligosarcosine conjugation. These results implied that intracellular processes, including the decondensation of pDNA, contributed to the efficiency of the protein expression from pDNA. This study demonstrated the advantages of oligosarcosine conjugation to Arg-rich CPPs and provided valuable insight into the future design of CPPs.
引用
收藏
页码:890 / 896
页数:7
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