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内质网靶向光动力疗法将肿瘤转化为原位治疗性肿瘤疫苗。

ER-Targeting PDT Converts Tumors into In Situ Therapeutic Tumor Vaccines.

作者信息

Liu Xu, Liu Yu, Li Xiang, Huang Jiaxin, Guo Xuemeng, Zhang Junlei, Luo Zhenyu, Shi Yingying, Jiang Mengshi, Qin Bing, Du Yongzhong, Luo Lihua, You Jian

机构信息

College of Pharmaceutical Sciences, Zhejiang University, 886 Yuhangtang Road, Hangzhou, Zhejiang 310058, People's Republic of China.

出版信息

ACS Nano. 2022 Jun 28;16(6):9240-9253. doi: 10.1021/acsnano.2c01669. Epub 2022 Jun 17.

Abstract

A therapeutic tumor vaccine is a promising approach to cancer treatment. One of its strategies is to treat patient-derived tumor cells in vitro and then administer them in vivo to induce an adaptive immune response and achieve cancer treatment. Here, we want to explore the possibility of converting cancer tissue into a therapeutic tumor vaccine through induced immunogenic cell death (ICD) in situ. We loaded indocyanine green (ICG) into liposomes (ICG-Lipo) and modified it with the pardaxin peptide to realize an endoplasmic reticulum (ER)-targeting function (Par-ICG-Lipo). A microfluidic technique was developed for loading ICG, a water-soluble molecule, into liposomes with a high encapsulation efficiency (greater than 90%). Under near-infrared (NIR) irradiation, ER-targeting photodynamic therapy (PDT) induced by Par-ICG-Lipo could promote the release of danger-signaling molecules (DAMPs) and tumor antigens (TAAs) in vivo, which significantly enhanced the immunogenicity in vivo and thus stimulates a strong antitumor immune response. This process would be further amplified by adopting dendritic cells. In general, our strategy transformed in situ tumor cells into therapeutic vaccines by ER-targeting PDT, which could provide a clinically applicable and effective approach for cancer treatment.

摘要

治疗性肿瘤疫苗是一种很有前景的癌症治疗方法。其策略之一是在体外处理患者来源的肿瘤细胞,然后在体内给予这些细胞以诱导适应性免疫反应并实现癌症治疗。在此,我们想要探索通过原位诱导免疫原性细胞死亡(ICD)将癌组织转化为治疗性肿瘤疫苗的可能性。我们将吲哚菁绿(ICG)载入脂质体(ICG-Lipo),并用豹蟾鱼毒素肽对其进行修饰,以实现内质网(ER)靶向功能(Par-ICG-Lipo)。开发了一种微流控技术,用于将水溶性分子ICG以高封装效率(大于90%)载入脂质体。在近红外(NIR)照射下,Par-ICG-Lipo诱导的内质网靶向光动力疗法(PDT)可促进体内危险信号分子(损伤相关分子模式,DAMPs)和肿瘤抗原(TAAs)的释放,这显著增强了体内免疫原性,从而刺激强烈的抗肿瘤免疫反应。采用树突状细胞可进一步放大这一过程。总体而言,我们的策略通过内质网靶向PDT将原位肿瘤细胞转化为治疗性疫苗,这可为癌症治疗提供一种临床适用且有效的方法。

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