DNA-GEL, Novel Nanomaterial for Biomedical Applications and Delivery of Bioactive Molecules

Enrico Lattuada,Debora Caprara,Antonella Stoppacciaro,Francesco Sciortino,Manuela Leo,Luisa Salvatori,Patrizia Filetici

doi:10.3389/fphar.2020.01345

Enrico Lattuada, Debora Caprara + Show 5 more

Open Access

https://doi.org/10.3389/fphar.2020.01345

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Abstract

Novel DNA materials promise unpredictable perspectives for applications in cell biology. The realization of DNA-hydrogels built by a controlled association of DNA nanostars, whose binding can be tuned with minor changes in the nucleotide sequences, has been recently described. DNA hydrogels, with specific gelation properties that can be reassambled in desired culture media supplemented with drugs, RNA, DNA molecules and other bioactive compounds offer the opportunity to develop a novel nanomaterial for the delivery of single or multiple drugs in tumor tissues as an innovative and promising strategy. We provide here a comprehensive description of different, recently realized DNA-gels with the perspective of stimulating their biomedical application. Finally, we discuss the possibility to design sophisticated 3D tissue-like DNA-gels incorporating cell spheroids or single cells for the assembly of a novel kind of cellular matrix as a preclinical investigation for the implementation of tools for in vivo delivery of bioactive molecules.

Highlights

The well-understood reversibility and programmability of the Watson-Crick pairing interactions have promoted DNA as a leading component for the realization of bottom-up materials at the nanoscale (Seeman, 2016)
The opportunity to play with a vast number of different oligomers makes it possible to generate DNA hydrogels differing in their local structure and functionality, from disordered networks resulting upon the spontaneous binding of randomly occurring sequences (Bellini et al, 2012) to the controlled formation of ordered networks composed of identical DNA nanoparticles, exploiting what is today called hierarchical multi-step self-assembly (Figures 1A, B)
A possible example is shown in Figure 1A, where four selected sequences hybridize to form a nanostar with four arms. This aggregation process is followed by an additional step in which the binding of the sticky overhangs – single-stranded DNA sequences located at the end of each arm – occurs (Figure 1B)

Summary

Introduction

The well-understood reversibility and programmability of the Watson-Crick pairing interactions have promoted DNA as a leading component for the realization of bottom-up materials at the nanoscale (Seeman, 2016). The possibility to design specific biofunctional sequences with stimuli-responsive properties led to the construction of biocompatible DNA-hydrogels for biomedical applications, which are stable under physiological conditions.

Results

Conclusion