Stimuli-responsive controlled-release system using quadruplex DNA-capped silica nanocontainers

Abstract

A novel proton-fueled molecular gate-like delivery system has been constructed for controlled cargo release using i-motif quadruplex DNA as caps onto pore outlets of mesoporous silica nanoparticles. Start from simple conformation changes, the i-motif DNA cap can open and close the pore system in smart response to pH stimulus. Importantly, the opening/closing and delivery protocol is highly reversible and a partial cargo delivery can be easily controlled at will. A pH-switchable nanoreactor has also been developed to validate the potential of our system for on-demand molecular transport. This proof of concept might open the door to a new generation of carrier materials and could also provide a general route to use other functional nucleic acids/peptide nucleic acids as capping agents in the fields of versatile controlled delivery nanodevices.

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

“…This strategy, developed by Qu and co-workers, was the first to introduce stimuli-responsive DNA sequences for reversible pore caping. 41,42 In one example the authors prepared a DNA-MSN hybrids bound through amide bonds using the 5'-(H 2 N-(CH 2 ) 6 -CCC TAA CCC TAA CCC TAA CCC)-3' sequence as pH dependent quadruplex strand. According to the published results the fluorescent probe Rhodamine B was efficiently retained within the pores at pH=5, where the duplex is favoured and released at pH=8, where the expanded conformation prevailed.…”

“…According to the published results the fluorescent probe Rhodamine B was efficiently retained within the pores at pH=5, where the duplex is favoured and released at pH=8, where the expanded conformation prevailed. 41 In an almost simultaneous contribution, the same group reported the use of DNA duplex forming strand 5'-(GCA TGA ATT CAT GC)-3' to modify MSNs 42 in order to build temperature dependent and reversible as pore gates; for this gating the authors employed the previously developed click methodology 30,43 ( Figure 3). Based on the quadruplex-folding, a pore capping pH-dependent conformational shift was reported by the Wang group, who developed a UV light triggered valve onto MSNs.…”

Drug delivery systems based on nucleic acid nanostructures

“…18A) [142]. This special secondary structure of DNA is comprised of a single strand that folds into a quadruplex through multiple cytidines that are protonated at acidic pH [143,144].…”

Zeolitic Imidazolate Framework-8 Capped Mesoporous Silica Nanoparticles for pH-Controlled Drug Release

“…[18][19][20] To date, much effort has been made to develop pH-triggered drug release systems using MSN as nanocarriers. [21][22][23][24][25][26][27] For example, Zou et al proposed a natural gelatin capped MSN for intracellular anticancer drug controlled release. 21 The gelatin capping layer could effectively block drug release at neutral pH, but the slightly acidic environment triggered drug release due to the enhanced electrostatic repulsion between the gelatin and MSN, resulting in uncapping of the gelatin layer.…”

“…21 Chen et al used i-motif quadruplex DNA to cap the mesopores of MSN and realized pH-controlled drug release based on the morphology change of the DNA chains. 22 Huang et al prepared graphene quantum dots (GQDs) grafted MSN nanocarriers (GQDs-MSN) through electrostatic interaction, and in vitro assay showed the release of aspirin from the aspirin-loaded GQDs-MSN was pH-dependent. 23 Recently, our group developed a potential pH-controlled protein drug delivery system based on aldehyde-functionalized dendritic MSN as nanocarriers.…”