Nanoparticles (NPs) decorated with a high density of DNA strands, also known as spherical nucleic acids (SNAs), are widely used in DNA-programmable assembly, sensing, imaging, and therapeutics. A regular SNA synthesis is very timeconsuming, which requires great caution to avoid NP aggregation. Herein we report an extremely simple, efficient, and scalable process to realize instant (in seconds) synthesis of SNAs with record-high DNA density. Our method relies on a rapid water removal from a DNA/NP mixture in contact with a butanol phase. This process generates a dehydrated "solid solution" that greatly accelerates DNA anchorage on NPs via Au−S bonding. Compared to a state-of-the-art DNA conjugation strategy in the literature, up to 3-time increase of DNA density is achieved by the instant dehydration in butanol (INDEBT). The ultradense DNA grafting is accomplished in a few seconds, which is highly hybridizable to form core−satellite assemblies. Our work turns SNA synthesis into an easy job, and enables future explorations of physical, chemical, and biological effects of SNAs with ultrahigh DNA density.

Over the past two decades, DNA has been demonstrated as a powerful, versatile building material in the construction of a wide range of functional nanostructures, nanodevices, molecular nanomachines, and nanowalkers, [1][2][3] which have broad potential applications in computing, nanoelectronic devices, biosensing, and intelligent drug delivery. [1][2][3][4] In particular, multiple DNA conjugated gold nanoparticles (DNA-GNPs) have recently emerged as an important class of nanomaterials for biodiagnosis and nanomedicine, due to a number of very attractive properties, including sharp melting transitions on binding to complementary DNA, enhanced target binding affi nity, high stability in high salt buffer, low/non-toxicity, resisting nuclease degradation, and effi cient uptake by some 50 different cell lines. [ 5 ] Polyvalent DNA-GNP conjugates have been used sucessfully in gene regulation, [ 6 ] and delivery of small molecule drugs [ 7 , 8 ] at the cellular level. To date, most DNA-GNP systems reported have simply used DNA as drug carrier, where the drug release was achieved by drug-DNA passive dissociation, [ 7 , 8 ] lacking stimuli responsive release which is important for effi cient drug delivery. Moreover, most GNP-DNA systems exibited limited stability in biological fl uids, showing a significant increase of carrier size in cell culture media (due to the non-specifi c adsorption of serum proteins), and could aggregate on cellular surfaces, which can limit their potential for in vivo applications. [5][6][7][8] On the other hand, pH is well-known to play a key role in many biological functions. Unlike healthy tissues which usually have a normal physiological pH of ∼ 7.4, disease regions such as tumors and intracellular endosomal/lysosomal compartments often exhibit abnormally high local acidities. [ 9 ] Therefore pH can be exploited as a useful strategy for cancer targeting. A proton-fuelled DNA nanomachine (PF-DNA) made of a single-stranded (ss) DNA of four stretches of cytosine ( C )-rich sequences ( i -motif domain), [ 10 ] fi rst proposed by Liu et al. [ 11 ] appears well-suited for cancer targeting. It can produce rapid, highly reversible conformational switches between a four-stranded i -motif structure at weakly acidic pH ( < 6.0) and random coil at higher pH ( > 6.4). [ 11 ] Previously, we and others have harnessed this pH-dependent conformational changes and successfully constructed several pH-responsive DNA nanostructures and nanodevices. [ 12 ] Herein, we report that this PF-DNA can be employed for effective delivery and pH-triggered release of doxorubicin (DOX), a model anticancer drug widely used in clinical treatment of various cancers, leukemia and Hodgkin's lymphoma, and also in drug delivery research (see Supporting Information (SI), Figure S1 for the number of drug delivery papers using DOX). Besides, being a DNA intercalator, DOX can be conveniently loaded to the PF-DNA system by simple mixing, avoiding the use of chemical conjugation or encapsulation steps which may affect its bioavailabilit...

Investigating how formamide forms in the interstellar medium is a hot topic in astrochemistry, which can contribute to our understanding of the origin of life on Earth.