Framework nucleic acids as programmable carrier for transdermal drug delivery

Christian Wiraja,Chenjie Xu,Daniel Chin Shiuan Lio,Chunhai Fan,David C Yeo,Mengjia Zheng,Ying Zhu,Maurice Van Steensel,Lihua Wang,Qian Li,Mo Xie,Weina Fang

doi:10.1038/s41467-019-09029-9

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.

Highlights

DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility
framework nucleic acids (FNAs) were examined through atomic force microscopy (AFM) or gel electrophoresis
We examined interaction of these FNAs with skin cells in vitro

Summary

Introduction

DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility. DNA origami based in vivo application has predominantly been explored through invasive needle injection In such systemic delivery, DNA structures are subjected to rapid disintegration and digestion besides immune- and renal-clearance, leading to low bioavailability at targeted sites[5,6]. The mechanism remains mostly unclear, the similarity of size and surface chemistry between FNAs and SNAs leads us to hypothesize that FNAs would penetrate the skin as well If successful, this attempt would provide an alternative carrier for TDD with precisely controlled size, shape and surface chemistry, while concurrently open new application route to circumvent the susceptibilities of FNAs in systemic drug delivery (Fig. 1). Compared with other topical carriers (i.e. liposomes and polymeric NPs), we observe twofold enhancements in DOX delivery and tumor inhibition, corroborating FNA efficacy in achieving TDD

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Conclusion