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Curated Papers > Recent high-impact research on the "tumor microenvironment" (IF≥30, last 5 years)

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

Literature Information ​

DOI10.1186/s12943-025-02270-5
PMID40033293
JournalMolecular cancer
Impact Factor33.9
JCR QuartileQ1
Publication Year2025
Times Cited9
KeywordsConjugational chemistry, Immunotherapy, Nanobody, Nanoparticle, Tumor microenvironment
Literature TypeJournal Article, Review
ISSN1476-4598
Pages65
Issue24(1)
AuthorsLiudmyla Maksymova, Yannick A Pilger, Lutz Nuhn, Jo A Van Ginderachter

TL;DR ​

This review discusses the potential of nanomedicines, particularly when combined with nanobodies, to improve cancer diagnosis and treatment by enhancing the precision of drug and imaging delivery while addressing off-target effects. It emphasizes the importance of understanding the tumor microenvironment and the development of smart nanoparticles for effective targeting and overcoming resistance mechanisms, ultimately aiming to improve therapeutic outcomes and patient responses.

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Conjugational chemistry · Immunotherapy · Nanobody · Nanoparticle · Tumor microenvironment

Abstract ​

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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Primary Questions Addressed ​

  1. What are the specific mechanisms by which nanobodies can modulate immune cell function in the tumor microenvironment?
  2. How do different types of nanoparticles influence the efficacy of nanobody-based therapies in cancer treatment?
  3. What are the current challenges in the formulation of nanoparticle-nanobody conjugates for clinical applications?
  4. How can the understanding of the tumor microenvironment inform the design of new nanomedicines for cancer therapy?
  5. In what ways can nanobody-nanoparticle formulations be optimized to overcome drug resistance in cancer therapies?

Key Findings ​

Research Background and Objectives ​

The review by Maksymova et al. (2025) focuses on the application of nanobodies in targeting the tumor microenvironment (TME) and their formulation as nanomedicines. The objective is to enhance cancer diagnostics and therapeutics by utilizing the unique properties of nanobodies, which are small, single-domain antibodies derived from camelids. The authors aim to discuss the current advancements in nanobody applications, particularly in cancer therapy, and explore how nanobody-nanoparticle conjugates can improve drug delivery and therapeutic efficacy.

Main Methods/Materials/Experimental Design ​

The review employs a comprehensive literature survey approach, summarizing various studies that investigate the targeting capabilities of nanobodies within the TME. Key methodologies include:

  • Nanobody Engineering: Modifications for improved specificity, stability, and affinity.
  • Nanoparticle Formulation: Different types of nanoparticles (inorganic, liposomes, biomaterials-derived carriers, synthetic organic nanoparticles) are explored for their ability to carry nanobodies and therapeutic agents.
  • Conjugation Chemistry: Techniques such as thiol-maleimide chemistry, click chemistry, and genetic engineering for precise attachment of nanobodies to nanoparticles.
Mermaid diagram

Key Results and Findings ​

  1. Nanobody Properties: Nanobodies exhibit high affinity and specificity, allowing them to target cryptic epitopes in the TME that conventional antibodies cannot access.
  2. Nanoparticle Utilization: Various nanoparticles, including liposomes and inorganic particles, can enhance the delivery of nanobodies and therapeutic agents, improving biodistribution and reducing systemic toxicity.
  3. Clinical Applications: Several nanobody-based therapeutics and diagnostics are in clinical trials, demonstrating efficacy in targeting specific tumor markers such as HER2, PD-L1, and CD206.

Main Conclusions/Significance/Innovation ​

The review concludes that nanobodies represent a promising avenue for improving cancer therapy due to their unique properties and versatility in targeting the TME. The integration of nanobodies with nanoparticles not only enhances therapeutic delivery but also provides opportunities for multimodal imaging and personalized medicine. The authors emphasize the potential of these technologies to revolutionize cancer treatment by addressing current limitations in specificity and efficacy.

Research Limitations and Future Directions ​

  • Limitations: The review acknowledges challenges in the clinical translation of nanobody-nanoparticle systems, including issues with scalability, batch-to-batch reproducibility, and the need for comprehensive safety evaluations.
  • Future Directions: Further research is needed to optimize targeting strategies, improve the pharmacokinetics of nanobody formulations, and explore the use of combination therapies to overcome resistance mechanisms in cancer treatment. Additionally, the development of personalized therapies based on tumor-specific biomarkers is highlighted as a crucial step forward.

This structured summary captures the essence of the review while highlighting the innovative potential of nanobodies in cancer therapy and diagnostics.

References ​

  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)

Literatures Citing This Work ​

  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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