Recent studies have shown that intradermal vaccination has great potential for T cell-mediated cancer immunotherapy. However, classical intradermal immunization with a hypodermic needle and syringe has several drawbacks. Therefore, in the present study a digitally controlled hollow microneedle injection system (DC-hMN-iSystem) with an ultra-low dead volume was developed to perform micro-injections (0.25–10 μL) into skin in an automated manner. A synthetic long peptide derived from human papilloma virus formulated in cationic liposomes, which was used as a therapeutic cancer vaccine, was administered intradermally by using the DC-hMN-iSystem. Fused silica hollow microneedles with an inner diameter of 50 μm and a bevel length of 66 ± 26 μm were successfully fabricated via hydrofluoric acid etching. Upon piercing these microneedles into the skin using a protrusion length of 400 μm, microneedles were inserted at a depth of 350 ± 55 μm. Micro-injections of 1–10 μL had an accuracy between 97 and 113% with a relative standard deviation (RSD) of 9%, and lower volumes (0.25 and 0.5 μL) had an accuracy of 86–103% with a RSD of 29% in ex vivo human skin. Intradermal administration of the therapeutic cancer vaccine via micro-injections induced strong functional cytotoxic and T-helper responses in mice, while requiring much lower volumes as compared to classical intradermal immunization. In conclusion, by using the newly developed DC-hMN-iSystem, very low vaccine volumes can be precisely injected into skin in an automated manner. Thereby, this system shows potential for minimally-invasive and potentially pain-free therapeutic cancer vaccination.

最近的研究表明，皮内接种疫苗对于T细胞介导的癌症免疫治疗具有巨大的潜力。然而，用皮下注射针头和注射器进行的经典皮内免疫有几个缺点。因此，在本研究中，开发了具有超低死体积的数控空心微针注射系统（DC-hMN-iSystem），以自动方式向皮肤进行微注射（0.25–10μL）。通过使用DC-hMN-iSystem皮内施用在阳离子脂质体中配制的源自人乳头瘤病毒的合成长肽，其被用作治疗性癌症疫苗。通过氢氟酸蚀刻成功地制造了熔融石英空心微针，其内径为50μm，斜角长度为66±26μm。使用400μm的突出长度将这些微针刺入皮肤后，以350±55μm的深度插入微针。微量进样1–10μL的准确度在97％至113％之间，相对标准偏差（RSD）为9％，较小体积的样品（0.25和0.5μL）的准确度在86–103％之间，RSD为29在离体人类皮肤中的百分比。通过显微注射对治疗性癌症疫苗进行皮内给药可在小鼠中引起强烈的功能性细胞毒性和T辅助反应，而与传统的皮内免疫相比，所需的体积要小得多。总之，通过使用新开发的DC-hMN-iSystem，可以自动方式将极少量的疫苗精确注射到皮肤中。因此，该系统显示出微创且可能无疼痛的治疗性癌症疫苗接种的潜力。