Framework nucleic acids as programmable carrier for transdermal drug delivery

Christian Wiraja, Ying Zhu, Daniel Chin Shiuan Lio, David C. Yeo, Mo Xie, Weina Fang, Qian Li, Mengjia Zheng, Maurice Steensel, Lihua Wang, Chunhai Fan () and Chenjie Xu ()
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Christian Wiraja: Nanyang Technological University
Ying Zhu: Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Daniel Chin Shiuan Lio: Nanyang Technological University
David C. Yeo: Nanyang Technological University
Mo Xie: Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Weina Fang: Shanghai Jiao Tong University
Qian Li: Shanghai Jiao Tong University
Mengjia Zheng: Nanyang Technological University
Maurice Steensel: Nanyang Technological University
Lihua Wang: Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Chunhai Fan: Shanghai Jiao Tong University
Chenjie Xu: Nanyang Technological University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09029-9

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