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Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models

Anane?Adjei, Akosua B.; Pearce, Amanda K.; Anane-Adjei, Akosua B.; Cavanagh, Robert J.; Monteiro, Patricia F.; Bennett, Thomas M.; Taresco, Vincenzo; Clarke, Phil A.; Ritchie, Alison A.; Alexander, Morgan R.; Grabowska, Anna M.; Alexander, Cameron

Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models Thumbnail


Authors

Akosua B. Anane?Adjei

Amanda K. Pearce

Akosua B. Anane-Adjei

Patricia F. Monteiro

Thomas M. Bennett

Phil A. Clarke

Alison A. Ritchie

ANNA GRABOWSKA anna.grabowska@nottingham.ac.uk
Professor of Cancer Microenvironment



Abstract

© 2020 Wiley-VCH GmbH The size, shape, and underlying chemistries of drug delivery particles are key parameters which govern their ultimate performance in vivo. Responsive particles are desirable for triggered drug delivery, achievable through architecture change and biodegradation to control in vivo fate. Here, polymeric materials are synthesized with linear, hyperbranched, star, and micellar-like architectures based on 2-hydroxypropyl methacrylamide (HPMA), and the effects of 3D architecture and redox-responsive biodegradation on biological transport are investigated. Variations in “stealth” behavior between the materials are quantified in vitro and in vivo, whereby reduction-responsive hyperbranched polymers most successfully avoid accumulation within the liver, and none of the materials target the spleen or lungs. Functionalization of selected architectures with doxorubicin (DOX) demonstrates enhanced efficacy over the free drug in 2D and 3D in vitro models, and enhanced efficacy in vivo in a highly aggressive orthotopic breast cancer model when dosed over schedules accounting for the biodistribution of the carriers. These data show it is possible to direct materials of the same chemistries into different cellular and physiological regions via modulation of their 3D architectures, and thus the work overall provides valuable new insight into how nanoparticle architecture and programmed degradation can be tailored to elicit specific biological responses for drug delivery.

Citation

Anane‚ÄźAdjei, A. B., Pearce, A. K., Anane-Adjei, A. B., Cavanagh, R. J., Monteiro, P. F., Bennett, T. M., …Alexander, C. (2020). Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models. Advanced Healthcare Materials, 9(22), Article 2000892. https://doi.org/10.1002/adhm.202000892

Journal Article Type Article
Acceptance Date Oct 6, 2020
Online Publication Date Oct 19, 2020
Publication Date Nov 18, 2020
Deposit Date Oct 7, 2020
Publicly Available Date Oct 20, 2021
Journal Advanced Healthcare Materials
Print ISSN 2192-2640
Electronic ISSN 2192-2659
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 9
Issue 22
Article Number 2000892
DOI https://doi.org/10.1002/adhm.202000892
Keywords biomedical applications, bionanotechnology, drug delivery, polymeric materials, stimuli?responsive materials
Public URL https://nottingham-repository.worktribe.com/output/4944205
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202000892

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