Fluorophore Selection and Incorporation Contribute to Permeation and Distribution Behaviors of Hyperbranched Polymers in Multi-Cellular Tumor Spheroids and Xenograft Tumor Models

Simpson, Joshua D; Monteiro, Patr�cia F; Ediriweera, Gayathri R; Sonderegger, Stefan E; Bell, Craig A; Fletcher, Nicholas L; Alexander, Cameron; Thurecht, Kristofer J

Abstract

Improving our understanding of how design choices in materials synthesis impact biological outcomes is of critical importance in the development of nanomedicines. Here, we show that fluorophore labeling of polymer nanomedicine candidates significantly alters their transport and cell association in multi-cellular tumor spheroids and their penetration in breast cancer xenografts, dependent on the type of the fluorophore and their positioning within the macromolecular structure. These data show the critical importance of the biomaterials structure and architecture in their tissue distribution and intracellular trafficking, which in turn govern their potential therapeutic efficacy. The broader implication of these findings suggests that when developing materials for medical applications, great care should be taken early on in the design process as relatively simple choices may have downstream impacts that could potentially skew preclinical biology data.

Citation

Simpson, J. D., Monteiro, P. F., Ediriweera, G. R., Sonderegger, S. E., Bell, C. A., Fletcher, N. L., …Thurecht, K. J. (2021). Fluorophore Selection and Incorporation Contribute to Permeation and Distribution Behaviors of Hyperbranched Polymers in Multi-Cellular Tumor Spheroids and Xenograft Tumor Models. ACS Applied Bio Materials, 4(3), 2675–2685. https://doi.org/10.1021/acsabm.0c01616

• Journal Article Type: Article
• Acceptance Date: Feb 16, 2021
• Online Publication Date: Feb 25, 2021
• Publication Date: Mar 15, 2021
• Deposit Date: Feb 17, 2021
• Publicly Available Date: Feb 26, 2022
• Journal: ACS Applied Bio Materials
• Print ISSN: 2576-6422
• Electronic ISSN: 2576-6422
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 3
• Pages: 2675–2685
• DOI: https://doi.org/10.1021/acsabm.0c01616
• Keywords: hyperbranched polymers; nanomedicine; fluorescence; multi-cellular tumour spheroid (MCTS) models; xenograft tumour models; bio-nano interactions
• Public URL: https://nottingham-repository.worktribe.com/output/5331315
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsabm.0c01616
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Bio Materials, copyright © 2021 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acsabm.0c01616.