PDF(Pubmed)
Abstract：
Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (μEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The μEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the μEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.
摘要：
尽管基于核酸的疫苗具有巨大的临床潜力，由于在人体内缺乏有效的局部基因递送技术，它们诱导治疗性免疫应答的功效受到限制。在这项研究中,我们开发了一种基于水凝胶的有机电子器件（μEPO），用于核酸的透皮递送和体内微阵列细胞电穿孔，它专门针对皮下抗原呈递细胞（APC）中DNA的一步转染，用于癌症免疫治疗。μEPO装置包含具有预包封的干燥DNA的微针形电极阵列。在与皮肤组织加压接触时，电极重新水合，电触发释放DNA，然后电穿孔附近的细胞，可实现表皮和上真皮层50%以上细胞的体内转染。作为一个概念证明,μEPO技术用于促进新抗原基因的透皮递送,以激活抗原特异性免疫应答,用于基于DNA疫苗接种策略的增强的癌症免疫治疗.在卵清蛋白（OVA）癌症疫苗模型中，我们表明，用OVA-DNA的APC的高效透皮转染诱导强大的细胞和体液免疫应答，包括抗原呈递和产生IFN-γ+细胞毒性T淋巴细胞，其剂量比现有的肌肉注射（IM）方法少10倍以上，并有效抑制啮齿动物的肿瘤生长。
