本项目针对癌症免疫治疗的关键难题，将仿病毒基因载体、近红外光热效应和聚合物微针贴片技术的优势有机结合，探索制备一种近红外光热协同增强的癌症基因免疫治疗微针贴片。研究将采用可溶解聚合物微针为平台，实现负载近红外光染料IR820和pPD-1质粒的仿病毒纳米载体在皮下黑色素瘤中的定位传递；并利用近红外光热辅助手段实现“一石二鸟”的近红外光热协同增强免疫治疗模式：一方面，通过本课题组特色性的近红外光热辅助跨膜技术增强pPD-1质粒的原位转染，有效阻断PD-1/PDL-1免疫检测点通路，解除肿瘤细胞的免疫“隐身”逃避能力；另一方面，深入研究近红外光热效应对肿瘤特异性抗原表达的影响规律，探索实现免疫检测点阻断和光热诱导增强抗癌免疫应答二元协同增强的可能性，为提高癌症免疫治疗的临床有效性提供切实可行的途径。

Cancer immunotherapy has been regarded as the next generation of cancer treatment strategy due to its great potential to inhibit metastases and prevent tumour relapses via stimulating the inherent immunological systems of the body to attack tumour cells. However, until now, most of those immune-therapeutic strategies still have limitations such as the possible immunotoxicity, individual variations in therapeutic responses, etc..We explore in the project to develop a new platform to enhance immunotherapy effect for melanoma by combining microneedle patch-assisted gene delivery with NIR photothermal therapy. A bioinspired nanocarrier encapsulated with IR820, a photothermal agent, and plasmid pPD-1 is designed to be delivered into the subcutaneous melanoma via a physiologically soluable microneedle patch. The near-infrared (NIR) irradiation will be explored as a "kill two birds with one stone" strategy to enhance immunotherapy effect: Firstly, the NIR photothermal effect will enhance membrane permeability of the cultured cells and the high­efficiency delivery of plasmid pPD-1 into cells, which will promote the in situ transfection of pPD-1 and effectively block the PD-1 / PDL-1 immune checkpoint pathways; Secondly, The NIR-triggered photothermal ablation of cancer cell can explore to generate tumour-associated antigens, which can show vaccine-like functions to generate anti-tumour immunological effects. The new cancer immunotherapy by combining microneedle patch-assisted gene delivery with NIR photothermal therapy might provide a new promises way to eliminate primary tumours, inhibit metastases, and prevent tumour relapses.