Hierarchical Fabrication of DNA Wireframe Nanoarchitectures for Efficient Cancer Imaging and Targeted Therapy

Abstract

Though small-molecule drugs play a crucial role in cancer treatment, intrinsic issues such as poor solubility and systematic toxicity have considerably mitigated their anticancer functions and caused unwanted side effects. To achieve satisfying therapeutic efficiency, it is essential to develop innovative targeting systems for precise and efficient delivery of anticancer drugs. In this work, a hierarchical selfassembly strategy was applied to fabricate a core−shell nanoarchitecture composed of a DNA octahedral wireframe and chemodrug-functionalized Sgc8c aptamer. The integrated enhanced permeability and retention effect of the DNA nanostructure and active targeting ability of the Sgc8c aptamer allowed the highly selective chemodrug delivery and in vivo efficient imaging and treatment. The advantage of our multifunctional nanostructure was further highlighted by its impressive serum stability, excellent accumulation ability, deep penetration capability, significantly improved therapeutic efficacy, and favorable biosafety. This study showed promising potential of such a core−shell DNA nanoarchitecture in precise drug loading control, drug delivery, and personal medicine.

Pharmaceutical applications of framework nucleic acids

“…Wang et al. 75 assembled a DNA octahedral framework composed of Sgc8c aptamers functionalized with combretastatin A-4 (a broad-spectrum microtubule inhibitor) for targeted cancer therapy.…”

Smart Drug Delivery Systems Based on DNA Nanotechnology

“…In addition to selective drug delivery, artificial DNA nanocarriers can also be applied to load specific diagnostic reagents to achieve nano‐theranostics, which combines early diagnosis with timely cancer treatment in an all‐in‐one platform [1] . In this section, we focus on the recent development of DNA nanostructures in cancer theranostics [1a,108] …”

DNA Nanodevice-Based Drug Delivery Systems

“…The G-C base pair of Dox embedded in the icosahedral can be controlled released by environmental pH, and after incubating with MUC1 positive cells, the intracellular internalization rate and cytotoxicity can be significantly improved. Lately, Tan [ 79 ] has adopted a layered self-assembly strategy and created a core-shell nanostructure consisting of a DNA octahedral framework and CA4-functionalized Sgc8c-aptamer (CA4-FS). CA4-FS can be loaded onto each side of the DNA frame, and a different number of CA4-FS can be accurately loaded onto the DNA octahedron by reasonable design ( Figure 5 a).…”

“…( a ) Six DNA tiles are layered and self-assembled to form an octahedral framework; after the nucleic acid aptamer is functionalized, single-chain handles connected on each side of the framework can be combined with a synthesized CA4-FS module; and with designing a sequence of the single-chain handles, different numbers of CA4-FS can be connected. The DNA nanocarrier in core-shell mode is finally formed, which is called CA4-Oct, reproduced with permission from Reference [ 79 ], Copyright 2020 American Chemical Society; ( b ) structural advantages: The outer three-dimensional spatial distribution of multivalent Sgc8c aptamers allows more precise binding to the tumor marker PTK7 receptor; enhanced permeability and retention (EPR) of passive targets improves delivery efficiency, reducing direct exposure of CA4 to avoid premature biotoxicity; the dense DNA octahedral framework facilitates the insertion of flexible CA4-FS into solid tumors to release the drug, reproduced with permission from Reference [ 79 ], Copyright 2020 American Chemical Society.…”