Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion-drug conjugates with cell-membrane affinity.

Animals Cell Membrane Endothelial Cells Mice Nanomedicine Neoplasms / drug therapy Pharmaceutical Preparations

Journal

Nature biomedical engineering

ISSN: 2157-846X

Titre abrégé: Nat Biomed Eng

Pays: England

ID NLM: 101696896

Informations de publication

Date de publication:
09 2021

Historique:

received: 24 04 2020

accepted: 16 02 2021

pubmed: 17 4 2021

medline: 18 1 2022

entrez: 16 4 2021

Statut: ppublish

Résumé

Effective anticancer nanomedicines need to exhibit prolonged circulation in blood, to extravasate and accumulate in tumours, and to be taken up by tumour cells. These contrasting criteria for persistent circulation and cell-membrane affinity have often led to complex nanoparticle designs with hampered clinical translatability. Here, we show that conjugates of small-molecule anticancer drugs with the polyzwitterion poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) have long blood-circulation half-lives and bind reversibly to cell membranes, owing to the negligible interaction of the polyzwitterion with proteins and its weak interaction with phospholipids. Adsorption of the polyzwitterion-drug conjugates to tumour endothelial cells and then to cancer cells favoured their transcytosis-mediated extravasation into tumour interstitium and infiltration into tumours, and led to the eradication of large tumours and patient-derived tumour xenografts in mice. The simplicity and potency of the polyzwitterion-drug conjugates should facilitate the design of translational anticancer nanomedicines.

Identifiants

DOI: 10.1038/s41551-021-00701-4 PMID: 33859387

pubmed: 33859387

doi: 10.1038/s41551-021-00701-4

pii: 10.1038/s41551-021-00701-4

doi:

Substances chimiques

Pharmaceutical Preparations 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1019-1037

Informations de copyright

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