← 返回前沿论文

化身原则:外泌体动力学指导肿瘤适应与下一代治疗策略

英文原题:The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.

查看英文原题

The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.

PubMed 2026/02/11(内容时间) J Nanobiotechnology Q1 · IF 15(JCR 2025)

研究概要

外泌体是纳米级细胞外囊泡,可转移蛋白质、核酸和脂质,反映其亲本细胞的状态。

中文摘要

外泌体是纳米尺度的细胞外囊泡,可转运蛋白质、核酸和脂质,并反映其母细胞状态。一个长期科学挑战是:肿瘤来源外泌体(TDE)可促进免疫逃逸、重塑肿瘤微环境并形成转移前生态位,加剧肿瘤侵袭性并削弱治疗效果,最终使晚期治疗选择收窄至姑息治疗。然而,TDE兼具免疫抑制作用和潜在治疗工具的双重角色,目前尚未充分纳入癌症免疫治疗框架。本综述考察TDE介导免疫抑制和治疗耐药的分子机制,并介绍利用或对抗外泌体生物学的工程策略。CAR-T细胞来源外泌体保留抗原特异性和细胞毒成分,却没有细胞失控增殖或细胞因子释放的风险,因此可能成为更安全的无细胞免疫疗法。基因工程、杂合囊泡设计和纳米技术进展已拓展外泌体用于递送CRISPR/Cas系统、化疗药物、免疫调节RNA及疫苗的应用;整合脂质体或纳米颗粒可进一步提高靶向性和疗效。仍待解决的问题包括缺乏标准化方案、生产规模化困难及监管框架尚未明确。借鉴《孙子兵法》,外泌体可被视作策略“化身”:它们是隐蔽的信使,既能瓦解宿主防御,也可能携带将免疫重新引向肿瘤的潜力。它们兼具隐匿与反击作用,展示了穿透隐蔽屏障、重塑治疗战场的能力,为精准癌症免疫治疗开辟新方向。

展开英文摘要原文

Exosomes are nanoscale extracellular vesicles that transfer proteins, nucleic acids, and lipids, reflecting the state of their parent cells. A persistent scientific challenge is that tumor-derived exosomes (TDEs) facilitate immune evasion, remodel the tumor microenvironment, and create premetastatic niches, intensifying tumor aggressiveness and undermining therapeutic efficacy, ultimately narrowing treatment options to palliative strategies in advanced settings. Yet their dual roles as suppressive agents and potential therapeutic tools remain poorly integrated within current cancer immunotherapy frameworks. This review examines the molecular mechanisms underlying TDE-mediated immune suppression and therapeutic resistance, while also highlighting engineering strategies to exploit or counteract exosome biology. Exosomes derived from chimeric antigen receptor (CAR) T cells preserve antigen specificity and cytotoxic components without the risks of uncontrolled proliferation or cytokine release, offering a safer class of cell free immunotherapies. Advances in genetic engineering, hybrid vesicle design, and nanotechnology have extended exosome applications to the delivery of CRISPR/Cas systems, chemotherapeutic agents, immunoregulatory RNAs, and vaccines, with liposome or nanoparticle integration enhancing targeting and efficacy. Remaining obstacles include the lack of standardized protocols, scalability issues in production, and unresolved regulatory frameworks. Drawing on The Art of War, exosomes can be envisioned as avatars of strategy, discreet messengers capable of undermining host defenses while simultaneously carrying the potential to redirect immunity against the tumor. By embodying both deception and counterattack, they illustrate the capacity to penetrate hidden barriers and redefine the therapeutic battlefield, opening new horizons for precision cancer immunotherapy.

论文信息

作者
Baena JC、Cabrera-Salcedo SC、Carrera Suárez Y、Biancha-Vasco JM、Rios-Serna LJ、García-Mantilla MD、Estrada-Schweineberg M、Victoria Hincapie JS
第一作者单位
Division of Oncology, Department of Medicine, Fundación Valle del Lili, ICESI University, Cali, Colombia. Juan.baena@fvl.org.co.
通讯作者单位
LiliCAR-T Group, Fundación Valle del Lili, ICESI, Cali, Colombia. sergio.cabrera.sa@fvl.org.co.
文献类型
综述
期刊
Journal of nanobiotechnology2026 Feb 11
原文标识
PubMed 41673677 · DOI 10.1186/s12951-026-04089-8