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Cancer nanomedicine

A nanoparticle’s pathway into tumours

Nature Materials volume 19, pages 486–487 (2020)Cite this article

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New evidence now suggests that the dominant mechanism of extravasation of nanoparticles into solid tumours may be through an active process of endothelial transcytosis.

The enhanced permeability and retention (EPR) effect has been the central paradigm supporting the formulation of nanomedicines to treat solid tumours since the late 1980s, when reports described preferential tumour extravasation of macromolecules in experimental animal models1,2. The increased permeability of the tumour vasculature has classically been attributed to the presence of large inter-endothelial gaps, a product of rapid and disorganized angiogenesis that supports tumour growth3. These leaky spots, together with poor lymphatic drainage and slower blood flow in tumours, were seen as an opportunity to enhance the passive diffusion and accumulation of chemotherapies and/or contrast agents when delivered by nanocarriers small enough to slip through the gaps. However, the impact at the patient’s bedside after three decades of research aiming to develop cancer nanomedicines has been disappointing. Less than ten anticancer drug delivery systems are currently in phase III or IV clinical trials and only ten have received regulatory approval in Europe and the United States, seven of which are liposomal formulations4,5,6. Thus, despite the wide variety of nanomaterials being tested at the bench, we have not witnessed significant innovation in the portfolio of clinically approved nanoformulations since Doxil (liposomal doxorubicin) received approval from the Food and Drug Administration in 1995. More strikingly, while most clinical-stage nanomedicines have been shown to improve the pharmacokinetics and ameliorate the side effects of free drug chemotherapies, increases in therapeutic efficacy and overall survival are very narrow even for the best performing formulations, and completely absent for most7.

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Fig. 1: Mechanisms of nanoparticle tumour extravasation.

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Authors and Affiliations

  1. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Irene de Lázaro & David J. Mooney

  2. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA

    Irene de Lázaro & David J. Mooney

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  1. Irene de Lázaro
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  2. David J. Mooney
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Correspondence to David J. Mooney.

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de Lázaro, I., Mooney, D.J. A nanoparticle’s pathway into tumours. Nat. Mater. 19, 486–487 (2020). https://doi.org/10.1038/s41563-020-0669-9

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