School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore, 637459, Singapore.
Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
Nat Commun. 2019 Mar 8;10(1):1147. doi: 10.1038/s41467-019-09029-9.
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.
DNA 纳米结构作为一种具有内在生物相容性、均一性和多功能性的药物载体具有广阔的应用前景。然而，在全身给药后，由于其在血清中迅速解体，导致在靶部位的生物利用度较低，从而限制了其在生物医学中的应用。本研究通过局部给药的方式展示了框架核酸（FNAs）的经皮传递。通过设计具有不同形状和大小的 FNAs，我们研究了它们在小鼠和人体皮肤外植体上的穿透情况。皮肤组织学显示出尺寸依赖性的穿透，尺寸≤75nm 的 FNAs 可有效地到达真皮层。17nm 的四面体 FNAs 显示出从皮肤边缘穿透到 350μm 的最大穿透深度。重要的是，在皮肤穿透过程中保持了结构的完整性。在小鼠黑素瘤模型中，与局部应用游离阿霉素、脂质体或聚合物纳米粒负载的阿霉素相比，负载阿霉素的 FNAs 的局部应用可使药物积累和肿瘤抑制作用提高 2 倍以上。在最小的全身生物分布下实现可编程穿透，突显了 FNA 作为局部经皮药物传递载体的潜力。
