You Qing, Wu Gege, Li Hui, Liu Jingyi, Cao Fangfang, Ding Lingwen, Liang Fuming, Zhou Bo, Ma Lilusi, Zhu Ling, Wang Chen, Yang Yanlian, Chen Xiaoyuan
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China.
Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Nat Nanotechnol. 2025 Jun 16. doi: 10.1038/s41565-025-01952-x.
Residual cancer stem-like cells (CSCs) can cause tumour recurrence within a narrow margin around the initial tumour resection lesion, increasing the risk of post-surgical relapse and incurability. Currently, there are no efficient strategies for tracking and eradicating CSCs. Here we propose a nanovaccine strategy, called NICER, based on a nanovesicle system integrating CSC-specific antigen display and epigenetic nano-regulator encapsulation with a dendritic-cell-targeting aptamer, to simultaneously eradicate CSCs and bulk tumour cells. Specifically, nanovesicles derived from aldehyde-dehydrogenase-overexpressing tumours could serve as integrated antigens carrying both CSC-specific antigen and tumour-associated antigen. Epigenetic nano-regulator targeting YTH N-methyladenosine RNA binding protein 1 could restrict dendritic cell lysosomal protease activity to modulate the effective cross-presentation of integrated antigens via major histocompatibility complex class I for immune responses. Overall, NICER represents a broad-spectrum vaccine approach against both CSCs and bulk tumours that can significantly inhibit postoperative cancer recurrence and metastasis, prolonging survival rates.
残留的癌症干细胞样细胞（CSCs）可在初始肿瘤切除病灶周围的狭小范围内导致肿瘤复发，增加术后复发和无法治愈的风险。目前，尚无有效追踪和根除CSCs的策略。在此，我们提出一种名为NICER的纳米疫苗策略，该策略基于一种纳米囊泡系统，将CSC特异性抗原展示、表观遗传纳米调节剂封装与树突状细胞靶向适体相结合，以同时根除CSCs和实体肿瘤细胞。具体而言，源自过表达醛脱氢酶的肿瘤的纳米囊泡可作为整合抗原，携带CSC特异性抗原和肿瘤相关抗原。靶向YTH N-甲基腺苷RNA结合蛋白1的表观遗传纳米调节剂可限制树突状细胞溶酶体蛋白酶活性，通过主要组织相容性复合体I类调节整合抗原的有效交叉呈递，以引发免疫反应。总体而言，NICER代表了一种针对CSCs和实体肿瘤的广谱疫苗方法，可显著抑制术后癌症复发和转移，延长生存率。
