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The following is a summary of “Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines,” published in the March 2025 issue of the Molecular Cancer by Maksymova et al.

Nanomedicine has emerged as a promising approach in the field of cancer theranostics, offering innovative strategies to enhance both diagnostic precision and therapeutic efficacy. One of the most significant advancements in this field is the integration of nanobodies with nanomedicines, which has the potential to improve the targeted delivery of drugs and imaging agents while minimizing off-target toxicities. The evolution of nanomedicine is further being propelled by the development of smart nanoparticles and their application in cancer immunotherapy. The success of nano-immunotherapy, however, is contingent on a comprehensive understanding of the tumor microenvironment, particularly the intricate mechanisms underlying cancer-induced immunosuppression and immune evasion. To achieve effective therapeutic targeting, it is essential to modulate immune cell function, overcome resistance mechanisms associated with stromal components and the extracellular matrix, and facilitate the direct elimination of malignant cells.

A crucial aspect of advancing cancer nanomedicine is the identification of key molecular targets that drive tumor progression and therapy resistance. The ability to pinpoint such molecules is fundamental for the development of innovative treatment strategies and diagnostic tools capable of predicting patient responses and monitoring therapeutic outcomes. Modern nanomedicines are designed with careful consideration of multiple factors, including the selection of suitable carriers that ensure biocompatibility, controlled drug release, and optimized pharmacokinetics. The integration of nanobodies in these formulations provides a unique advantage due to their small size, high stability, and exceptional binding specificity to biological targets. Their ability to penetrate dense tumor tissues and bind to antigens with high affinity makes them ideal candidates for enhancing the precision of cancer immunotherapies.

This review provides an in-depth analysis of the latest applications of nanobody-based strategies in targeting various components of the tumor microenvironment for both therapeutic and diagnostic purposes. Researchers also examine the primary types of nanoparticles used as carriers for cancer immunotherapy and discuss innovative approaches for the development of nanobody-nanoparticle conjugates. Additionally, investigators highlight how these conjugates enhance the functionality of current nanomedicines by improving tumor targeting, enhancing immune responses, and overcoming drug resistance. By leveraging the synergy between nanobodies and nanoparticles, next-generation nanomedicines have the potential to revolutionize cancer treatment, offering more precise, efficient, and personalized therapeutic strategies for improved patient outcomes.

Source: molecular-cancer.biomedcentral.com/articles/10.1186/s12943-025-02270-5