Self‐Assembly of Supramolecular DNA Amphiphiles through Host–Guest Interaction and Their Stimuli‐Responsiveness

Abstract

micelles, [6] nanofibers, [7] vesicles, [8] and nanosheets. [9] More interestingly, morphological shift of the DNA assemblies has been achieved through external stimuli, such as pH values, [10] temperature, [11] DNA-selective enzymatic activity, [12] and host-guest recognition. [13] Recently, supramolecular host-guest chemistry has been an effective strategy to construct supra-amphiphiles [14] by conjugating hydrophilic and hydrophobic segments. These supra-amphiphiles can assemble into diverse stimuli-responsive nanomaterials, applied in materials science, [15] supramolecular catalysis, [16] and biochemistry. [17] Doubtlessly, the hostguest approach could be an ideal alternative to construct DNA supra-amphiphiles. To date, the construction of DNA supra-amphiphiles through host-guest interactions has been rarely reported. [18] Moreover, the effect of such different topologic guests or stimuli-responsive guests on the assembled morphology is still unknown.Herein, we design and construct two DNA supra-amphiphiles via noncovalent recognition based on the host-guest interaction between cucurbit[7]uril (CB[7]) and the guests (ferrocene derivative or adamantane derivative). The host-guest interaction between CB[7] and guest (ferrocene or adamantane) has been widely investigated in the supramolecular chemistry due to their efficient molecular recognition with a strong association constant (K a = 10 4 -10 6 M −1 for CB [7] and ferrocene analogs, [19] K a = 10 8 -10 13 M −1 for CB [7] and adamantine derivates [20] ). Here, CB[7]-modified DNA (D18-CB[7]) is regarded as the hydrophilic host. Two types of molecules with different guest units and topologic structures are chosen to be the hydrophobic guests. One is ferrocene modified with second-generation poly(benzyl ether) dendron (G1) and the other is adamantane tailed with three 18-carbon alkyl chains (G2). Through host-guest interaction, the supramolecular DNA amphiphiles could be modularly constructed and then undergo their self-assembly process (Scheme 1). The self-assembly mechanism and application of the assembled nanostructures have been further demonstrated. Finally, the stimuli-responsiveness of assemblies induced by competitive guest or by the redox properties of ferrocene has been investigated.After having the host and two different guests obtained, we want to explore the construction of DNA-based supra-amphiphiles (D18-CB[7]/G1 and D18-CB[7]/G2) through host-guest 2000022 (5 of 5) www.advancedsciencenews.com www.mrc-journal.de

DNA Strand Displacement Driven by Host–Guest Interactions

“…The CB[7]–guest interaction is especially adaptable to aqueous/biological systems due to (a) the small size of the interaction partners (e.g., compared to streptavidin or antibody-based binding), (b) the range of dissociation constants that can be dialed-in ( K d ∼ 10 –2 –10 –17 M), (c) the synthetic ease/scalability of host/guest moieties, and (d) the established bioorthogonality of CB[7]–guest interactions. − To employ CB[7] chemistry within a DNA scaffold, straightforward strategies to access oligonucleotides conjugated to CB[7] and guest head-groups are needed. − In this work, the CB[7]–DNA conjugates were prepared, by following a report published by our group, wherein monoazido-functionalized CB[7] is reacted with hexynyl-DNA via copper-catalyzed alkyne–azide click (CuAAC) chemistry . The synthetic guest molecules attached to the DNA were synthesized by standard NHS-ester/amine coupling reactions.…”

Aptamer-functionalized fluorine-containing DNAsomes for targeted drug delivery to cancer cells

“…4-Aminophenol, 4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecyl iodide, N,N-diisopropylethylamine, N,N-dimethylformamide (DMF), ethyl acetate (EtOAc), petroleum ether, sodium sulphate (Na 2 SO 4 ), N,N 0 -methylene diacrylamide, acrylamide (AM), ammonium persulfate, N,N,N 0 ,N 0 -tetramethylethylenediamine, 2-cyanoethyl N,Ndiisopropylchlorophosphoramidite, dichloromethane, sodium chloride, natrium bicarbonate and doxorubicin (DOX) were obtained from Aladdin Reagent Co., Ltd (Shanghai, China). Reagents and drugs related to cell experiments are purchased directly from different companies: 1640 RPMI cell culture medium, DMEM/high glucose, fetal bovine serum (FBS) (Gibco Invitrogen, USA), penicillin and streptomycin, DAPI staining solution (Beyotime Co., Ltd, China), 2Â Urea-TBE loading buffer (DNA denaturation) (Solarbio Co., Ltd, China), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (Energy Chemical Co., Ltd, China).…”

“…For DNA amphiphilic compounds, it is usually the fatty alkyl chain that acts as the hydrophobic group. [9][10][11] In addition to the natural lipid alkyl chain, perfluorinated substituted alkyl chains with higher hydrophobicity 12 are also used as hydrophobic groups. Fluorinated vesicles (F-vesicles) are a type of nano-assemblies composed of amphiphilic molecules consisting of hydrophilic polar head groups and hydrophobic fluorinated alkyl chains.…”

Cucurbiturils in nucleic acids research

“…Very recently, the same group developed stimuli-responsive DNA-based micelles constructed of CB [7]-modified DNA oligonucleotides 59 and two types of hydrophobic guests such as dendrimer-appended ferrocene 60 and adamantane derivative 61 functionalized with alkyl tails (Scheme 13). 96 Host-guest complexation between the CB [7] functionality and guest entities yielded supramolecular amphiphilic complexes 59-60 and 59-61 that further assembled into spherical micelles with a diameter of about 18 and 30 nm, respectively, as shown by TEM analysis. The micelles could encapsulate the hydrophobic dye Nile Red, on one hand, and anchor DNA-conjugated Aunanoparticles through DNA hybridization, on the other hand, which proved that 60 or 61 formed the core whereas DNA strands were located at a periphery of the micelles.…”