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Obstacles and opportunities in a forward vision for cancer nanomedicine

Abstract

Cancer nanomedicines were initially envisioned as magic bullets, travelling through the circulation to target tumours while sparing healthy tissues the toxicity of classic chemotherapy. While a limited number of nanomedicine therapies have resulted, the disappointing news is that major obstacles were overlooked in the nanoparticle’s journey. However, some of these challenges may be turned into opportunities. Here, we discuss biological barriers to cancer nanomedicines and elaborate on two directions that the field is currently exploring to meet its initial expectations. The first strategy entails re-engineering cancer nanomedicines to prevent undesired interactions en route to the tumour. The second aims instead to leverage these obstacles into out-of-the-box diagnostic and therapeutic applications of nanomedicines, for cancer and beyond. Both paths require, among other developments, a deeper understanding of nano–bio interactions. We offer a forward look at how classic cancer nanomedicine may overcome its limitations while contributing to other areas of research.

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Fig. 1: Elapsed time from first clinical trial to FDA approval of cancer nanomedicines.
Fig. 2: Biological barriers to systemically administered nanomedicines with intracellular targets in cancer cells.
Fig. 3: Novel applications of cancer nanomedicines based on what have previously been considered undesired interactions with biological barriers.

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Acknowledgements

We acknowledge funding from the National Cancer Institute of the National Institutes of Health under award numbers U01CA214369 and U54CA244726. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We apologize to colleagues whose relevant publications were not cited due to space limitations.

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I.d.L. and D.J.M. conceived and wrote the manuscript.

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de Lázaro, I., Mooney, D.J. Obstacles and opportunities in a forward vision for cancer nanomedicine. Nat. Mater. (2021). https://doi.org/10.1038/s41563-021-01047-7

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