Challenges and Perspectives of DNA Nanostructures in Biomedicine

Abstract

DNA nanotechnology holds substantial promise for future biomedical engineering and the development of novel therapies and diagnostic assays. The subnanometer‐level addressability of DNA nanostructures allows for their precise and tailored modification with numerous chemical and biological entities, which makes them fit to serve as accurate diagnostic tools and multifunctional carriers for targeted drug delivery. The absolute control over shape, size, and function enables the fabrication of tailored and dynamic devices, such as DNA nanorobots that can execute programmed tasks and react to various external stimuli. Even though several studies have demonstrated the successful operation of various biomedical DNA nanostructures both in vitro and in vivo, major obstacles remain on the path to real‐world applications of DNA‐based nanomedicine. Here, we summarize the current status of the field and the main implementations of biomedical DNA nanostructures. In particular, we focus on open challenges and untackled issues and discuss possible solutions.

Phthalocyanine–DNA origami complexes with enhanced stability and optical properties

“…This highly anionic biopolymer strongly binds to 1, which release the intact 6HB (5). Finally, 1-6HB was subjected to the same digestion conditions (6) and subsequently treated with heparin, resulting in the recovery of intact 6HB (7). To prove that the DO protection is achieved solely through the interaction with 1, and not due to the macroscopic complexation or aggregation, the same experiment was repeated in the presence of 200 mM NaCl yielding the same result (Fig.…”

“…These 2D and 3D DO 2 can carry out predefined tasks, such as controlled drug delivery, targeting and release of cargo. [3][4][5][6][7] However, DNAalbeit otherwise being a biocompatible molecule -can be digested or denatured under challenging conditions. For example, foreign DNA from pathogens and damaged endogenous DNA are detected and degraded via complex pathways.…”

Increasing Complexity in Wireframe DNA Nanostructures

“…However, some obstacles and open questions still remain on the way toward revolutionizing implementations, especially in biomedicine [38,99]. The stability of the wireframe structures seems to be rather different compared to the DNA structures designed in particular on 3D lattices [50,69,74], but interestingly, there are also reports suggesting that 2D DNA origami or rolled sheets may survive in physiological conditions for several hours [100,101].…”

“…Some wireframe shapes can be folded in low-magnesium or low-sodium conditions, and they have also elicited better stability in biological cell-compatible buffers, such as phosphate buffered saline, when contrasted with their lattice-based companions [50,69,74]. The other important issues are their partially unknown sequence-and superstructure-dependent drug-loading properties [38,102]-as well as susceptibility to nucleases [103,104]. Unfortunately, it is extremely hard to make comparisons between different design strategies and DNA shapes as the conditions vary between each reported study.…”

“…Nevertheless, the rapid constantly cheapening synthesis of custom DNA sequences [9] and the development of new design methods [8]-in particular, the modular DNA origami technique [10][11][12][13], user-friendly computer-aided design software [14][15][16], and advanced simulation tools [17][18][19][20][21][22]-have all driven the evolution of structural DNA nanotechnology. As of today, programmable DNA nanostructures [23,24] may find uses in a variety of applications [23][24][25], ranging from materials science, nanofabrication, photonics, and microscopy [26][27][28][29][30][31][32] to robotics, therapeutics, and diagnostics [33][34][35][36][37][38].…”