Synthesis and Applications of Stimuli‐Responsive DNA‐Based Nano‐ and Micro‐Sized Capsules

Abstract

Stimuli-responsive, drug-loaded, DNA-based nano-and micro-capsules attract scientific interest as signal-triggered carriers for controlled drug release. The methods to construct the nano-/micro-capsules involve i) the layer-by-layer deposition of signal-reconfigurable DNA shells on drugloaded microparticles acting as templates, followed by dissolution of the core templates; ii) the assembly of three-dimensional capsules composed of reconfigurable DNA origami units; and iii) the synthesis of stimuli-responsive drug-loaded capsules stabilized by DNA−polymer hydrogels. Triggers to unlock the nano-/micro-capsules include enzymes, pH, light, aptamer−ligand complexes, and redox agents. The capsules are loaded with fluorescent polymers, metal nanoparticles, proteins or semiconductor quantum dots as drug models, with anti-cancer drugs, e.g., doxorubicin, or with antibodies inhibiting cellular networks or enzymes over-expressed in cancer cells. The mechanisms for unlocking the nano-/micro-capsules and releasing the drugs are discussed, and the applications of the stimuli-responsive nano-/microcapsules as sense-and-treat systems are addressed. The scientific challenges and future perspectives of nano-capsules and micro-capsules in nanomedicine are highlighted. Drug Delivery groups or duplex DNA or G-quadruplex by photoactive groups may lead to the triggered separation of duplex DNA or G-quadruplex structures ( Figure 1D). For example, disulfide bridges were reported to stabilize DNA duplex structures, while the reduction of the disulfide by thiols led to the separation of the duplex structures. [24][25][26] Also, trans-azobenzene photoisomerizable units linked covalently to duplex nucleic acids or associated with G-quadruplexes via supramolecular interactions, were reported to stabilize these structures, while the cis-azobencene units lack binding affinities (or stabilization effects) to these structures. [27][28][29][30] Photoisomerization of the trans-azobenzene units to the cis-azobenzene configuration, which lacks affinity toward the duplex DNA, results in the release of the photoactive units, in the weakening of the duplex structures, and eventually in their separation. By the cyclic photoisomerization of the photoactive azobenzene units, the double-stranded nucleic acid is then switched between stable and less stable configurations. Alternatively, photodegradable o-nitrobenzyl phosphate ester groups can be incorporated into the duplex DNA structure, and the light-induced separation of the phosphate units may lead to the separation of the duplex DNA. [31] Finally, sequence-specific nucleic acids, known as aptamers, reveal selective recognition properties toward low-molecular-weight substrates (e.g., ATP, cocaine) [32,33] or macromolecular ligands (e.g., thrombin, VEGF). [34,35] The formation of high-affinity complexes between the aptamer and the ligand may then provide a mechanism to separate duplex nucleic acid hybrids [36] (Figure 1E).The structural features of nucleic acids and the possibilities to reconfigure DNA ...

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Multifunctional DNA Nanogels for Aptamer‐Based Targeted Delivery and Stimuli‐Triggered Release of Cancer Therapeutics

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Molecular bionics – engineering biomaterials at the molecular level using biological principles

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