Aptamer‐modified tetrahedral DNA nanostructure‐immobilized liposome for specific gene delivery and potential cancer theragnostic

Abstract

Targeted delivery of therapeutic agents to cancer cells is crucial for effective cancer treatment without adverse effects. In this study, we developed a novel delivery carrier, Aptamer‐modified tetrahedral DNA nanostructure (TDN) immobilized Liposome (ApTL), for specific delivery to nucleolin‐overexpressing cancer cells. We demonstrated that targeted ApTL was highly effective in delivering plasmid and mRNA to nucleolin‐overexpressing cancer cells compared to non‐targeted ApTL with a non‐specific aptamer. ApTL, which is highly negative and nano‐sized, specifically delivered nucleic acids to MDA‐MB‐231 and HeLa cancer cells, primaily via lipid‐raft‐mediated endocytosis. Furthermore, the co‐delivery of mRNA and doxorubicin resulted in increased apoptosis and reduced cancer cell viability. Interestingly, co‐delivery of mRNA and Dox did not show a significant difference in EGFP expression at 24 h but dramatically increased EGFP expression at 48 h, making ApTL/mEGFP/Dox a promising candidate for detecting live cancer cells after targeted cancer drug treatment. Our results suggest that ApTL can be a promising tool for the targeted delivery of therapeutic agents to nucleolin‐overexpressing cancer cells, providing a new strategy for cancer theragnostic.This article is protected by copyright. All rights reserved

DNA-Based Nanostructured Platforms as Drug Delivery Systems

“…Herein, aptamer-modified tetrahedron directed the delivery to nucleolin overexpressing cancer cells via lipid-raft-mediated endocytosis. 41 The DNA nanostructures equipped with lipids can result in a system with a high drug carrying capability. Willem simple to functionalize and can be loaded with drug molecules.…”

“…Lim and Hwang designed DNA nanostructure immobilized liposomes for co-delivery of mRNA and doxorubicin to cancer cells. Herein, aptamer-modified tetrahedron directed the delivery to nucleolin overexpressing cancer cells via lipid-raft-mediated endocytosis …”

Recent advances in the synthesis of single‐stranded DNA in vitro

“…[11,12] For short ssDNA (10-100 nt of the length), also called oligonucleotides, phosphoramidite based chemical synthesis received widespread attention due to its low cost, high speed, and high efficiency. [6,13] However, the error rate of the sequence increases with the length, which made it difficult to synthesize ssDNA fragments longer than 150 nt. [14,15] To solve this bottleneck, several methods have been developed, including chemical synthesis, enzyme synthesis, and isothermal synthesis.…”