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文献精选 > 近年高分"肿瘤微环境"研究（IF≥30，近5年）

Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines. ​

文献信息 ​

DOI10.1186/s12943-025-02270-5
PMID40033293
期刊Molecular cancer
影响因子33.9
JCR 分区Q1
发表年份2025
被引次数9
关键词结合化学, 免疫疗法, 纳抗体, 纳米颗粒, 肿瘤微环境
文献类型Journal Article, Review
ISSN1476-4598
页码65
期号24(1)
作者Liudmyla Maksymova, Yannick A Pilger, Lutz Nuhn, Jo A Van Ginderachter

一句话小结 ​

本综述探讨了纳米药物与纳米抗体在癌症治疗与诊断中的应用，强调其在提高药物递送精确性和克服耐药机制方面的潜力。研究表明，深入理解肿瘤微环境及关键分子的作用是开发高效疗法和监测患者治疗反应的关键，为未来的癌症免疫治疗提供了新思路。

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结合化学 · 免疫疗法 · 纳抗体 · 纳米颗粒 · 肿瘤微环境

摘要 ​

在癌症治疗和诊断的新兴策略中，纳米药物在推动患者的诊断和治疗方面展现出显著的潜力。结合纳米抗体，纳米药物有望提高药物或成像剂递送的精确性和效率，从而解决当前方法中的关键局限性，如非靶向毒性。智能纳米颗粒的开发及其与免疫治疗的结合将进一步加速纳米药物的发展。显然，纳米免疫治疗的成功将依赖于对肿瘤微环境的全面理解，包括推动癌症介导的免疫抑制和免疫逃逸的机制之间复杂的相互作用。因此，有效的肿瘤微环境治疗靶向需要调节免疫细胞功能，克服与基质成分或细胞外基质相关的耐药机制，和/或直接消除癌细胞。因此，识别在癌症进展和耐药过程中涉及的关键分子对开发有效的疗法和诊断工具至关重要，这些工具能够预测患者对治疗的反应并监测治疗结果。目前的纳米药物在设计时仔细考虑了诸如载体的选择（例如，生物相容性、可控药物释放）和靶向部分等因素。纳米抗体的独特性质使其成为以高亲和力和特异性靶向生物分子的有效工程工具。在本综述中，我们重点介绍纳米抗体在靶向肿瘤微环境各组成部分的最新应用，以用于诊断和治疗目的。我们还探讨了作为癌症免疫治疗载体的主要类型纳米颗粒，以及纳米颗粒-纳米抗体偶联物的制备策略。最后，我们强调纳米抗体-纳米颗粒配方如何增强当前的纳米药物。

英文摘要 ​

Among the emerging strategies for cancer theranostics, nanomedicines offer significant promise in advancing both patients' diagnosis and treatment. In combination with nanobodies, nanomedicines can potentially enhance the precision and efficiency of drug or imaging agent delivery, addressing key limitations of current approaches, such as off-target toxicities. The development of nanomedicines will be further accelerated by the creation of smart nanoparticles, and their integration with immunotherapy. Obviously, the success of nano-immunotherapy will depend on a comprehensive understanding of the tumor microenvironment, including the complex interplay of mechanisms that drive cancer-mediated immunosuppression and immune escape. Hence, effective therapeutic targeting of the tumor microenvironment requires modulation of immune cell function, overcoming resistance mechanisms associated with stromal components or the extracellular matrix, and/or direct elimination of cancer cells. Identifying key molecules involved in cancer progression and drug resistance is, therefore, essential for developing effective therapies and diagnostic tools that can predict patient responses to treatment and monitor therapeutic outcomes. Current nanomedicines are being designed with careful consideration of factors such as the choice of carrier (e.g., biocompatibility, controlled cargo release) and targeting moiety. The unique properties of nanobodies make them an effective engineering tool to target biological molecules with high affinity and specificity. In this review, we focus on the latest applications of nanobodies for targeting various components of the tumor microenvironment for diagnostic and therapeutic purposes. We also explore the main types of nanoparticles used as a carrier for cancer immunotherapies, as well as the strategies for formulating nanoparticle-nanobody conjugates. Finally, we highlight how nanobody-nanoparticle formulations can enhance current nanomedicines.

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主要研究问题 ​

  1. 在纳米抗体的应用中，如何评估其对肿瘤微环境中不同细胞类型的特异性？
  2. 纳米药物在治疗癌症中的应用，如何解决肿瘤微环境带来的免疫逃逸问题？
  3. 目前有哪些新型纳米颗粒载体被开发用于提高纳米抗体的靶向性和生物相容性？
  4. 纳米抗体与传统抗体相比，在肿瘤治疗中具有什么样的优势和潜在局限？
  5. 在开发针对肿瘤微环境的纳米药物时，如何识别和选择关键的靶分子以提高治疗效果？

核心洞察 ​

研究背景和目的 ​

近年来，肿瘤微环境（TME）在癌症治疗中的重要性日益凸显。纳米药物结合纳米抗体的使用，为癌症的靶向治疗和成像提供了新的可能性。本研究旨在探讨纳米抗体在靶向肿瘤微环境中的应用及其作为纳米药物的制备策略，以期提高癌症治疗的精准性和有效性。

主要方法/材料/实验设计 ​

本研究采用以下技术路线：

Mermaid diagram
  1. 纳米抗体设计：选择合适的纳米抗体，基于其对特定肿瘤相关分子的高亲和力和特异性。
  2. 选择靶标分子：通过分析肿瘤微环境中表达的关键分子，确定靶标。
  3. 纳米载体选择：评估不同类型的纳米载体（如无机纳米粒子、脂质体、聚合物载体等），选择最适合的载体。
  4. 纳米抗体-纳米载体结合：采用不同的化学方法（如点击化学、巯基-马来酰亚胺反应）进行结合。
  5. 靶向药物释放：评估纳米载体在肿瘤微环境中的药物释放效率。
  6. 评估治疗效果：通过体内外实验评估治疗效果。
  7. 临床应用：总结临床试验结果，探索纳米药物的临床转化。

关键结果和发现 ​

  • 纳米抗体因其小尺寸和高特异性，能够有效穿透肿瘤组织，靶向特定的肿瘤细胞。
  • 纳米载体的选择显著影响纳米抗体的靶向性和药物释放效率，聚合物载体表现出更好的生物相容性和控制释放能力。
  • 在多项前临床和临床试验中，纳米抗体结合纳米载体的疗法显示出良好的抗肿瘤效果，特别是在靶向肿瘤微环境中的免疫细胞和基质细胞。

主要结论/意义/创新性 ​

本研究表明，纳米抗体与纳米载体的结合为肿瘤微环境的靶向治疗提供了新的策略。通过优化纳米药物的设计，可以显著提高治疗的精准性和降低副作用。这一方法不仅有助于改善现有癌症治疗的效果，还可能推动新型免疫疗法的发展。

研究局限性和未来方向 ​

尽管纳米抗体和纳米载体的结合显示出良好的治疗潜力，但仍存在一些局限性：

  • 靶标选择的复杂性：肿瘤微环境的异质性使得靶标选择变得复杂，可能影响治疗效果。
  • 临床转化的挑战：从实验室到临床的转化过程仍需大量的时间和资源。

未来的研究应集中在以下几个方向：

  • 深入理解肿瘤微环境的复杂性，以优化靶标选择。
  • 开展更多的临床试验，以验证纳米药物的有效性和安全性。
  • 探索新型的纳米载体和结合策略，以提高治疗的针对性和效果。

参考文献 ​

  1. Evaluation of nanobody-based biologics targeting purinergic checkpoints in tumor models in vivo. - Mélanie Demeules;Allan Scarpitta;Romain Hardet;Henri Gondé;Catalina Abad;Marine Blandin;Stephan Menzel;Yinghui Duan;Björn Rissiek;Tim Magnus;Anna Marei Mann;Friedrich Koch-Nolte;Sahil Adriouch - Frontiers in immunology (2022)
  2. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience. - Jill Adler-Moore;Richard T Proffitt - The Journal of antimicrobial chemotherapy (2002)
  3. Potential role of immunotherapy and targeted therapy in the treatment of cancer: A contemporary nursing practice. - Hamad Ghaleb Dailah;Abdullah Abdu Hommdi;Mahdi Dafer Koriri;Essa Mohammed Algathlan;Syam Mohan - Heliyon (2024)
  4. Proteomic Profiling of Extracellular Matrix Components from Patient Metastases Identifies Consistently Elevated Proteins for Developing Nanobodies That Target Primary Tumors and Metastases. - Noor Jailkhani;Karl R Clauser;Howard H Mak;Steffen Rickelt;Chenxi Tian;Charles A Whittaker;Kenneth K Tanabe;Stephen R Purdy;Steven A Carr;Richard O Hynes - Cancer research (2023)
  5. Naturally occurring antibodies devoid of light chains. - C Hamers-Casterman;T Atarhouch;S Muyldermans;G Robinson;C Hamers;E B Songa;N Bendahman;R Hamers - Nature (1993)
  6. Surface functionalization of exosomes using click chemistry. - Tyson Smyth;Krastina Petrova;Nicole M Payton;Indushekhar Persaud;Jasmina S Redzic;Michael W Graner;Peter Smith-Jones;Thomas J Anchordoquy - Bioconjugate chemistry (2014)
  7. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. - Marie Scully;Spero R Cataland;Flora Peyvandi;Paul Coppo;Paul Knöbl;Johanna A Kremer Hovinga;Ara Metjian;Javier de la Rubia;Katerina Pavenski;Filip Callewaert;Debjit Biswas;Hilde De Winter;Robert K Zeldin; - The New England journal of medicine (2019)
  8. Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer. - Tianhang Zhai;Chao Wang;Yifeng Xu;Weifeng Huang;Zhijun Yuan;Tao Wang;Shuang Dai;Shaogang Peng;Tuling Pang;Wenchao Jiang;Yuhua Huang;Yuefeng Zou;Yingda Xu;Joanne Sun;Xinjiang Gong;Jinping Zhang;Andy Tsun;Bin Li;Xiaoniu Miao - Journal for immunotherapy of cancer (2021)
  9. Immunogenicity Risk Profile of Nanobodies. - Chloé Ackaert;Natalia Smiejkowska;Catarina Xavier;Yann G J Sterckx;Sofie Denies;Benoit Stijlemans;Yvon Elkrim;Nick Devoogdt;Vicky Caveliers;Tony Lahoutte;Serge Muyldermans;Karine Breckpot;Marleen Keyaerts - Frontiers in immunology (2021)
  10. Targeted delivery of organic small-molecule photothermal materials with engineered extracellular vesicles for imaging-guided tumor photothermal therapy. - Yafang Dong;Peng Xia;Xiaolong Xu;Jing Shen;Youbin Ding;Yuke Jiang;Huifang Wang;Xin Xie;Xiaodong Zhang;Weihua Li;Zhijie Li;Jigang Wang;Shan-Chao Zhao - Journal of nanobiotechnology (2023)

引用本文的文献 ​

  1. Nanomedicine in Cancer Therapeutics: Current Perspectives from Bench to Bedside. - K M Abdullah;Gunjan Sharma;Ajay P Singh;Jawed A Siddiqui - Molecular cancer (2025)
  2. Application of Nanodrug Delivery Systems in Enhancing Treatment of Gastritis and Gastric Cancer: A Systematic Evaluation of Targeted Therapy. - Miaomiao Xu;Shujie Tian;Jing Wang;Shuqing Gan;Ziting Zhang;Lixing Weng - Pharmaceutics (2025)
  3. Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery. - Kyunghee Noh;Soyeon Yi;Hyeran Kim;Jieun Lee;Suhyeon Kim;Wonbeak Yoo;Eunkyeong Jung;Jinsol Choi;Hwangseo Park;Seungha Hwang;Jin Young Kang;Kwang-Hyun Park;Heewon Park;Yong-Kyu Lee;Eun-Kyung Lim;Taejoon Kang;Juyeon Jung - Signal transduction and targeted therapy (2025)
  4. Targeted disruption of phage liquid crystalline droplets abolishes antibiotic tolerance of bacterial biofilms. - Abul K Tarafder;Miles Graham;Luke K Davis;Shawna Pratt;Jan Böhning;Pavithra Manivannan;Zhexin Wang;Camila M Clemente;Raymond J Owens;George A O'Toole;Philip Pearce;Tanmay A M Bharat - bioRxiv : the preprint server for biology (2025)
  5. Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies. - Jingnan Xue;Longhao Zhang;Kai Zhang;Kai Zhou;Haitao Zhao - Frontiers in immunology (2025)
  6. Trends and hotspots in research related to tumor immune escape: bibliometric analysis and future perspectives. - Houcheng Zhu;Yue Huang;Xiangjin Wang;Wang Xiang;Yong Xie - Frontiers in immunology (2025)
  7. Gold nanoparticles in the diagnosis and treatment of ovarian and cervical cancers: a comprehensive understanding. - Senhui Zhang;Tong Li;Deshuo Jiang;Hengmei Shi;Huyang Hou;Ziyi Fu;Xiaoyan Shi - Frontiers in oncology (2025)
  8. Modulating Subcellular Localization to Preserve the Stability and Functionality of Intracellular Nanobodies. - Wenli Sun;Keke Huang;Yaping Cheng;Ailing Huang;Yu Kong;Jun Lu;Tianlei Ying;Yanling Wu - Antibodies (Basel, Switzerland) (2025)
  9. Mechanisms and applications of epigenome editing in plants: current status, challenges and future perspectives. - Asmamaw Menelih;Abayeneh Girma;Akale Assamere - Functional & integrative genomics (2025)

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