A DNA-Based Nanocarrier for Efficient Gene Delivery and Combined Cancer Therapy

Abstract

The efficient delivery of a therapeutic gene into target tissues has remained a major obstacle in realizing a viable gene-based medicine. Herein, we introduce a facile and universal strategy to construct a DNA nanostructure-based codelivery system containing a linear tumor therapeutic gene (p53) and a chemotherapeutic drug (doxorubicin, DOX) for combined therapy of multidrug resistant tumor (MCF-7R). This novel codelivery system, which is structurally similar to a kite, is rationally designed to contain multiple functional groups for the targeted delivery and controlled release of the therapeutic cargoes. The self-assembled DNA nanokite achieves efficient gene delivery and exhibits effective inhibition of tumor growth in vitro and in vivo without apparent systemic toxicity. These structurally and chemically well-defined codelivery nanovectors provide a new platform for the development of gene therapeutics for not only cancer but also a wide range of diseases.

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

“…d) Combination of gene‐/chemotherapy for multidrug resistant tumor MCF‐7 cells using a DNA nanostructure loading DOX and p53 in vivo, along with in vivo biodistribution imaging of Cy5.5‐labeled single‐strand DNA, of TOP (TO with p53 gene only) without aptamer, and of TOP with aptamer in MCF‐7R‐tumor‐bearing nude mice. Reproduced with permission . Copyright 2018, American Chemical Society.…”

“…Aptamers were also conjugated to functional materials by an amide linker or sulfonamide linker . However, complementary base pairing for conjugating aptamers to materials was shown as an effective alternative strategy for in vivo applications with appropriate stability . Non‐covalent methods were also employed to coat aptamers to the surface of 2D MoS 2 flakes .…”

Nucleic Acid–Based Functional Nanomaterials as Advanced Cancer Therapeutics

“…Ding and coworkers have developed a series of DNA origami as nanocarriers for drug delivery . For example, they reported two types of DNA origami nanostructures, a tubular shape and a triangular shape, for DOX delivery ( Figure a) .…”

Multifunctional DNA Origami Nanoplatforms for Drug Delivery

“…Reproduced from Ref. with permission from the American Chemical Society, Copyright 2018. c) DNA origami for Dox and RNAi codelivery. Reproduced from Ref.…”

“…P53, as an important tumor suppressor gene, plays a key role in the inhibition of the proliferation of tumor cells. Ding and co‐workers fabricated a triangular DNA origami containing a linear tumor therapeutic gene (p53) and a chemotherapeutic drug (Dox) for combined therapy of multidrug‐resistant tumors (Figure b) . The aptamer‐modified kitelike DNA origami nanoplatform demonstrated efficient gene‐delivery efficacy and exhibited high inhibition of multidrug‐resistant tumor growth in vivo without apparent systemic toxicity.…”