Light-Responsive and pH-Responsive DNA Microcapsules for Controlled Release of Loads

Abstract

A method to assemble light-responsive or pH-responsive microcapsules loaded with different loads (tetramethylrhodamine-modified dextran, TMR-D; microperoxidase-11, MP-11; CdSe/ZnS quantum dots; or doxorubicin-modified dextran, DOX-D) is described. The method is based on the layer-by-layer deposition of sequence-specific nucleic acids on poly(allylamine hydrochloride)-functionalized CaCO3 core microparticles, loaded with the different loads, that after the dissolution of the core particles with EDTA yields the stimuli-responsive microcapsules that include the respective loads. The light-responsive microcapsules are composed of photocleavable o-nitrobenzyl-phosphate-modified DNA shells, and the pH-responsive microcapsules are made of a cytosine-rich layer cross-linked by nucleic acid bridges. Irradiating the o-nitrobenzyl phosphate-functionalized microcapsules, λ = 365 nm, or subjecting the pH-responsive microcapsules to pH = 5.0, results in the cleavage of the microcapsule shells and the release of the loads. Preliminary studies address the cytotoxicity of the DOX-D-loaded microcapsules toward MDA-MB-231 breast cancer cells and normal MCF-10A breast epithelial cells. Selective cytotoxicity of the DOX-D-loaded microcapsules toward cancer cells is demonstrated.

Simulative and Experimental Characterization of a pH-Dependent Clamp-like DNA Triple-Helix Nanoswitch

“…The flexibility and modularity of this mechanism permits the fine tuning of the reactivity of different nanomaterials and nanodevices toward pH as demonstrated in recent works. 3,23,24,36 The computational and experimental data presented here indicate that the system is able to form a stable triple helix at pH 5.0, while at pH 8.0 there is no presence of …”

DNA Microcapsule for Photo‐Triggered Drug Release Systems

“…Several stimuli-responsive devices based on conventional delivery platforms such as liposomes and micelles have been reported. [24][25][26] In addition, DNA-layered CaCO 3 microparticles with various sensing units [27,28] and spherically arranged drug-conjugated DNA having redox sensing systems have been demonstrated. [29] Thus, the installation of stimuli-responsive devices on DNA microcapsules has the potential for therapeutic utility for spatiotemporal drug delivery.…”

pH- and ligand-induced release of loads from DNA–acrylamide hydrogel microcapsules

“…The synthesis of stimuli-responsive or stimuli-degradable loaded microcapsules is particularly interesting for controlled drug release applications. 9 Different triggers, such as heat, 10 light, 11 pH, 12 magnetic fields, 13 and chemical and biochemical reactions, 14 have been used to degrade the microcapsules and release the loads. Similarly, the preparation of hydrogel-stabilized loaded microcapsules has been reported, and the degradation of the hydrogel boundary was suggested as a mechanism for releasing the loads.…”

“…Furthermore, by the integration of stimuli-responsive nucleic acid units into the DNA shells of the microcapsules, signal-triggered degradable microcapsules have been designed. For example, photodegradable nucleic acids, 11 pH-responsive nucleic acids (i-motifs, triplexes), 11 and ligand–aptamer complexes 16,17 have been used to degrade all-DNA-based microcapsules and to release the loads. The all-DNA-stabilized microcapsules suffer, however, from several limitations, which include the complex layer-by-layer deposition ( via hybridization) of the functional nucleic acid layers, the single-cycle triggered unlocking of the microcapsules, which prevents switchable dose-controlled release of the loads, the sensitivity of the microcapsules to heat, the susceptibility of the microcapsules to enzymatic digestion, e.g.…”

“…18 Different triggers such as pH, 19 metal ions/ligands, 20 K + /crown ethers, 21 and light 11 have been used to stimulate hydrogel-to-solution transitions. Recently, a method of assembling thin films of stimuli-responsive hydrogels on surfaces was developed.…”