Abstract
DNA therapy for cancer requires efficient, selective and safe DNA delivery systems. Compared with other non-viral methods such as lipid or polymer-based DNA delivery vectors, peptide-based DNA delivery systems are biocompatible and biodegradable, which leads to lower immunogenicity and lower toxicity. Moreover, peptide vectors are easier to produce and their compositions easier to control because solid-phase peptide synthesis has been extensively developed. However, peptide-based systems for DNA delivery toward special tumor cells or tissues are still lacking. In this study, we constructed a non-viral 9rR-LTVSPWY peptide-based DNA delivery system and showed that it is able to efficiently and selectively transfect DNA into targeted tumor cells. This work presents a novel strategy for tumor cell-specific DNA delivery and a reference for designing more efficient DNA delivery systems targeted towards various types of cancer.
Highlights
DNA therapy for cancer requires efficient and safe systems that can deliver the therapeutic DNA selectively into targeted tumor cells
The N/P ratios represent the molar ratio of the arginines in 9rR to the phosphorus content in the DNA [19]
Characterization of 9rR-LTVSPWY/pDNA complexes Our previous study has indicated that the replacement of L-Arg residues with D-Arg residues imparts greater proteolytic resistance of oligoarginine peptides [26]
Summary
DNA therapy for cancer requires efficient and safe systems that can deliver the therapeutic DNA selectively into targeted tumor cells. Viral vectors have been used to transfer genes into cancer cells successfully [1,2,3,4] These vectors have serious disadvantages, such as limited loading capacity, complexity of production, innate immunogenicity, and the risk of inflammatory responses and toxicity, that limit their clinical applications [5,6]. Of the existing non-viral vectors, cationic lipids and cationic polymers are the most intensively studied and frequently employed. They have dose-dependent toxicities in in vivo applications [7,8]
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