Qu Moyuan, Kim Han-Jun, Zhou Xingwu, Wang Canran, Jiang Xing, Zhu Jixiang, Xue Yumeng, Tebon Peyton, Sarabi Shima A, Ahadian Samad, Dokmeci Mehmet R, Zhu Songsong, Gu Zhen, Sun Wujin, Khademhosseini Ali
Department of Bioengineering, Center for Minimally Invasive Therapeutics, California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nanoscale. 2020 Aug 28;12(32):16724-16729. doi: 10.1039/d0nr02759f. Epub 2020 Aug 12.
The skin houses a developed vascular and lymphatic network with a significant population of immune cells. Because of the properties of the skin, nucleic acid delivery through the tissue has the potential to treat a range of pathologies, including genetic skin conditions, hyperproliferative diseases, cutaneous cancers, wounds, and infections. This work presents a gelatin methacryloyl (GelMA) microneedle (MN)-based platform for local and controlled transdermal delivery of plasmid DNA (pDNA) with high transfection efficiency both in vitro and in vivo. Intracellular delivery of the nucleic acid cargo is enabled by poly(β-amino ester) (PBAE) nanoparticles (NPs). After being embedded in the GelMA MNs, sustained release of DNA-encapsulated PBAE NPs is achieved and the release profiles can be controlled by adjusting the degree of crosslinking of the GelMA hydrogel. These results highlight the advantages and potential of using PBAE/DNA NP-embedded GelMA MN patches (MN/PBAE/DNA) for successful transdermal delivery of pDNA for tissue regeneration and cancer therapy.
皮肤拥有发达的血管和淋巴网络，以及大量免疫细胞。由于皮肤的特性，通过该组织进行核酸递送有潜力治疗一系列病症，包括遗传性皮肤病、过度增殖性疾病、皮肤癌、伤口和感染。这项工作展示了一种基于甲基丙烯酰化明胶（GelMA）微针（MN）的平台，用于在体外和体内高效转染的质粒DNA（pDNA）的局部和可控透皮递送。核酸货物的细胞内递送由聚（β-氨基酯）（PBAE）纳米颗粒（NP）实现。嵌入GelMA微针后，可实现包裹DNA的PBAE NPs的持续释放，并且可以通过调节GelMA水凝胶的交联程度来控制释放曲线。这些结果突出了使用嵌入PBAE/DNA NP的GelMA微针贴片（MN/PBAE/DNA）成功透皮递送pDNA用于组织再生和癌症治疗的优势和潜力。
