Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination

• 成果类型: Article
• 署名作者: Wang, Yuan; Qu, Jin; Xiong, Chuxiao; Chen, Bing; Xie, Kai; Wang, Mingxue; Liu, Zhen; Yue, Zhao; Liang, Zhenghua; Wang, Feng; Zhang, Tianlong; Zhu, Guangyu; Kuang, Yi Becki; Shi, Peng
• 署名单位: City University of Hong Kong; City University of Hong Kong; City University of Hong Kong; Hong Kong University of Science & Technology; Hong Kong University of Science & Technology; City University of Hong Kong; City University of Hong Kong; Shenzhen Research Institute, City University of Hong Kong
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10466
• DOI: 10.1073/pnas.2322264121
• 发表日期: 2024-06-18
• 关键词: microneedle patch; vaccines; delivery; skin; release; DRUG

摘要

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 ( mu EPO) 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 mu EPO 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 mu EPO 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 -gamma + 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.