Framework nucleic acids as programmable carrier for transdermal drug delivery

Abstract

DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility. However, rapid serum disintegration leads to low bioavailability at targeted sites following systemic administration, hindering their biomedical applications. Here we demonstrate transdermal delivery of framework nucleic acids (FNAs) through topical applications. By designing FNAs with distinct shapes and sizes, we interrogate their penetration on mice and human skin explant. Skin histology reveals size-dependent penetration, with FNAs ≤75 nm effectively reaching dermis layer. 17 nm-tetrahedral FNAs show greatest penetration to 350 µm from skin periphery. Importantly, structural integrity is maintained during the skin penetration. Employing a mouse melanoma model, topical application of doxorubicin-loaded FNAs accommodates ≥2-fold improvement in drug accumulation and tumor inhibition relative to topically-applied free doxorubicin, or doxorubicin loaded in liposomes and polymeric nanoparticles. Programmable penetration with minimal systemic biodistribution underlines FNA potential as localized transdermal drug delivery carriers.

Size-selective molecular recognition based on a confined DNA molecular sieve using cavity-tunable framework nucleic acids

“…Inspired by this interesting and important approach, herein we developed a DNA molecular sieve for the size-selective recognition to improve the biosensing selectivity and accuracy. Framework nucleic acids, which involve the rational design of DNA nanostructures based on the high predictability of Watson-Crick base pairing, provide the ability for high controllability and nanometer precision [23][24][25][26][27][28][29][30][31] . In particular, with the programmable and precise control of their size, shape, and binding sites, framework nucleic acids enable the precise and site-specific functionalization of guest objects [32][33][34][35][36][37][38][39][40][41] , including inorganic nanoparticles, nucleic acids, enzymes, hydrophobic micelles, and so on.…”

Challenges and Perspectives of DNA Nanostructures in Biomedicine

“…Therapeutic Applications Doxorubicin (DOX) is widely and commercially used in cancer therapy-especially for solid tumors-and it is awellknown DNAi ntercalator by its nature.T herefore,a tl east in principle,i ts hould be one of the most promising candidates for DN-based delivery,a si tc an be loaded into customized nanostructures that may have ap lethora of other functions. There are multiple examples of DN that have been employed as DOX carriers such as DNAt etrahedra (DT), [10,11] twisted 3D DO, [12] DO triangles, [13][14][15] rectangles, [11] and helix bundles, [13] as well as tubular DO loaded into liposomes. [16] In addition to DOX, its close molecular relative daunorubicin has also been used as ad rug for a( Tr ojan) "DNAh orse".…”

“…[16] In addition to DOX, its close molecular relative daunorubicin has also been used as ad rug for a( Tr ojan) "DNAh orse". [17] Although the efficacyofDOX-loaded DNAnanocarriers was verified in several in-vivo models, [10,11,13,14,16] each approach has its own and different loading and purification strategy, environment, pH, as well as DOX and ion concentrations, thus making the results extremely hard to compare to each other. Not only are the spectroscopic [18] properties of DOX strongly ion-and pH-dependent, [19] but DOX is also commonly employed in substantial excess to DN in the loading process,a lthough it is known to self-aggregate at high concentrations.…”

Controlling wireframe DNA origami nuclease degradation with minor groove binders

“…DNA nanostructures have further been deployed in a variety of preliminary studies as therapeutic delivery platforms. These applications include the controlled organization of antigens to activate B cells 14 , the delivery of siRNA [15][16] , CpG oligonucleotides 17 and small molecules drugs [18][19][20] . Logicgated nanorobots have been leveraged to to achieve controlled cargo release in vitro 21 and in vivo 1 .…”