ATP-responsive DNA-graphene hybrid nanoaggregates for anticancer drug delivery

Abstract

Stimuli-triggered drug delivery systems are primarily focused on the applications of the tumor microenvironmental or cellular physiological cues to enhance the release of drugs at the target site. In this study, we applied adenosine-5′-triphosphate (ATP), the primary “energy molecule”, as a trigger for enhanced release of preloaded drugs responding to the intracellular ATP concentration that is significantly higher than the extracellular level. A new ATP-responsive anticancer drug delivery strategy utilizing DNA-graphene crosslinked hybrid nanoaggregates as carriers was developed for controlled release of doxorubicin (DOX), which consists of graphene oxide (GO), two single-stranded DNA (ssDNA, denoted as DNA1 and DNA2) and ATP aptamer. The single-stranded DNA1 and DNA2 together with the ATP aptamer serve as the linkers upon hybridization for controlled assembly of the DNA-GO nanoaggregates, which effectively inhibited the release of DOX from the GO nanosheets. In the presence of ATP, the responsive formation of the ATP/ATP aptamer complex causes the dissociation of the aggregates, which promoted the release of DOX in the environment with a high ATP concentration such as cytosol compared with that in the ATP-deficient extracellular fluid. This supports the development of a novel ATP-responsive platform for targeted on-demand delivery of anticancer drugs inside specific cells.

Endogenous Stimuli-responsive Nanocarriers for Drug Delivery

“…60 The system successfully achieved the targeted delivery of liposomal ATP and promoted the release of drug from the liposome, exhibiting highly therapeutic efficiency in cancer therapy. ATP-sensitive systems can also be adopted in nanocarriers such as CdSe/ZnS quantum dots, 61 DNAgraphene crosslinked hybrid nanoaggregates, 62 aptamergated Au nanocages, 63 mesoporous silica nanoparticles, 64 and so on. In particular, mesoporous silica nanoparticles are one of the most commonly adopted nanocarrier to construct ATP controlled-release system based on aptamer-target interactions.…”

ATP-mediated Release of a DNA-binding Protein from a Silicon Nanoneedle Array

“…30 Electrochemistry, 84(5), 305-307 (2016) minutes incubation was sufficient for binding of ATP (2.5-10 mM) to the aptamer moiety as reported in the previous studies. 13,20,21 Since the concentration of ATP in a cell is assumed to be 1-10 mM, 9,10 we had expected that in vivo ZFP release could be achieved by binding of intracellular ATP.…”

“…12,13 However, there are few reports describing protein delivery. Protein delivery is important both for diagnostics and for genome manipulation with DNA binding molecules such as Zinc-finger proteins (ZFPs).…”

Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA

“…21 Thus, it is still of great challenge to explore more facial and efficient stimuli-responsive nanocarriers, especially for achieving the co-delivery of drug and gene. Recently, adenosine triphosphate (ATP)-responsive nanocarriers for co-delivering drugs and genes have been successfully developed, [20][21][22][23][24][25][26][27] based on the higher ATP concentration in the intracellular fluids (1-10 mM) than in the extracellular environment (,0.4 mM). 28,29 For instance, Mo et al 20 constructed an ATP-triggered nanocarrier for doxorubicin (DOX) release through an ATP-responsive duplex (the ATP aptamer and its complementary single-stranded DNA), whose GC-rich motif was used to intercalate DOX into the aptamer duplex.…”