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Targeting metastasis with nanomedicine

Nature Reviews Bioengineering volume 4, pages 47–66 (2026)Cite this article

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Abstract

Metastatic cancer remains difficult to treat. Nanomedicine formulations can accumulate in primary tumours and metastases and can be designed to target key components of the metastatic cascade, including cancer cell invasion, intravasation, circulation, extravasation and colonization. Eight antimetastatic nanomedicines are approved for clinical use, more than twenty antimetastatic nanomedicines are currently explored in clinical trials and various designs are preclinically explored. In this Review, we outline key in vitro and in vivo models to study metastatic cancer and discuss how the different steps of the metastatic cascade can be targeted by nanomedicines. Furthermore, we highlight the design of antimetastatic nanomedicines for tumour microenvironment modulation, active targeting, stimuli-responsive drug release, multidrug combination therapy, RNA delivery and immunotherapy. Finally, we explore key future milestones in this field, emphasizing the importance of patient stratification in the clinical testing and translation of antimetastatic nanomedicines.

Key points

  • Metastases cause most cancer deaths; yet, their onset and spread remain poorly understood, and preclinical studies mainly focus on primary tumors, creating a gap towards developing effective treatments against metastasis.

  • Preclinical models, ranging from in vitro platforms to animal systems, and offering trade-offs between experimental throughput and biological relevance, are essential to study the metastatic cascade and identify therapeutic targets.

  • Cancer nanomedicines, like most standard anticancer therapies, are not designed to target metastases and antimetastatic pathways, leaving ample room for better understanding drug targeting to and treatment of metastatic cancers.

  • Several nanomedicines are being developed to use strategies that extend beyond traditional EPR-based passive drug targeting, including stimuli-responsive and actively targeted systems, nucleic acid delivery, multidrug combinations, and nano-immunotherapy.

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Fig. 1: Primary tumour and metastasis incidence.
Fig. 2: The metastatic cascade and potential targets for therapeutic intervention.
Fig. 3: Preclinical models to study metastasis.
Fig. 4: Next-generation antimetastatic nanomedicines.

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Acknowledgements

This work was funded by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia (MKW) under the Excellence Strategy of the Federal Government and the Länder through the Junior Principal Investigator (JPI) Fellowship, by the European Research Council (ERC CoG 864121, Meta-Targeting), by the European Commission (EuroNanoMed-III: NSC4DIPG), and by the German Research Foundation (DFG: GRK 2375 (grant no. 331065168), KFO 5011 and SFB 1066).

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  1. These authors contributed equally: Roger M. Pallares, Lorena Consolino, Alec Wang, Federica De Lorenzi.

Authors and Affiliations

  1. Institute for Experimental Molecular Imaging, Center for Biohybrid Medical Systems, Medical Faculty, RWTH Aachen University, Aachen, Germany

    Roger M. Pallares, Lorena Consolino, Alec Wang, Federica De Lorenzi, Fabian Kiessling & Twan Lammers

  2. The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion — Israel Institute of Technology, Haifa, Israel

    Avi Schroeder

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Contributions

R.M.P., L.C. and T.L conceived the project and were involved in all the phases of the preparation of the manuscript. R.M.P., L.C., A.W. and F.D. wrote the manuscript. L.C, A.W. and F.D designed the figures. R.M.P. designed the tables. All authors edited the manuscript.

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Pallares, R.M., Consolino, L., Wang, A. et al. Targeting metastasis with nanomedicine. Nat Rev Bioeng 4, 47–66 (2026). https://doi.org/10.1038/s44222-025-00358-7

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