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ER-Targeting PDT Converts Tumors into In Situ Therapeutic Tumor Vaccines
ACS Nano ( IF 15.8 ) Pub Date : 2022-06-17 , DOI: 10.1021/acsnano.2c01669
Xu Liu 1 , Yu Liu 1 , Xiang Li 1 , Jiaxin Huang 1 , Xuemeng Guo 1 , Junlei Zhang 1 , Zhenyu Luo 1 , Yingying Shi 1 , Mengshi Jiang 1 , Bing Qin 1 , Yongzhong Du 1 , Lihua Luo 1 , Jian You 1
Affiliation  

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.

中文翻译:

靶向 ER 的 PDT 将肿瘤转化为原位治疗性肿瘤疫苗

治疗性肿瘤疫苗是一种很有前途的癌症治疗方法。其策略之一是在体外治疗患者来源的肿瘤细胞,然后在体内给药以诱导适应性免疫反应并实现癌症治疗。在这里,我们想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) 加载到脂质体 (ICG-Lipo) 中,并用 pardaxin 肽对其进行修饰,以实现内质网 (ER) 靶向功能 (Par-ICG-Lipo)。开发了一种微流体技术,用于将 ICG(一种水溶性分子)装载到脂质体中,具有高封装效率(大于 90%)。在近红外 (NIR) 照射下,Par-ICG-Lipo诱导的ER靶向光动力疗法(PDT)可促进体内危险信号分子(DAMPs)和肿瘤抗原(TAAs)的释放,显着增强体内免疫原性,从而激发强大的抗肿瘤免疫力回复。该过程将通过采用树突状细胞进一步放大。总的来说,我们的策略通过靶向 ER 的 PDT 将原位肿瘤细胞转化为治疗性疫苗,这可以为癌症治疗提供一种临床适用且有效的方法。
更新日期:2022-06-17
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