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Carboxylated Cy5-labeled comb polymers passively diffuse the cell membrane and target mitochondria
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Mahmoud, Ayaat M., de Jongh, Patrick A. J. M., Briere, Sibylle, Chen, Moore Z., Nowell, Cameron J., Johnston, Angus P. R., Davis, Thomas P., Haddleton, David M. and Kempe, Kristian (2019) Carboxylated Cy5-labeled comb polymers passively diffuse the cell membrane and target mitochondria. ACS Applied Materials & Interfaces, 11 (34). pp. 31302-31310. doi:10.1021/acsami.9b09395 ISSN 1944-8252.
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WRAP-Carboxylated-Cy5-labeled-polymers-passively-mitochondria-Haddleton-2019.pdf - Accepted Version - Requires a PDF viewer. Download (1766Kb) | Preview |
Official URL: https://doi.org/10.1021/acsami.9b09395
Abstract
A detailed understanding of the cellular uptake and trafficking of nanomaterials is essential for the design of “smart” intracellular drug delivery vehicles. Typically, cellular interactions can be tailored by endowing materials with specific properties, for example, through the introduction of charges or targeting groups. In this study, water-soluble carboxylated N-acylated poly(amino ester)-based comb polymers of different degree of polymerization and side-chain modification were synthesized via a combination of spontaneous zwitterionic copolymerization and redox-initiated reversible addition–fragmentation chain-transfer polymerization and fully characterized by 1H NMR spectroscopy and size exclusion chromatography. The comb polymers showed no cell toxicity against NIH/3T3 and N27 cell lines nor hemolysis. Detailed cellular association and uptake studies by flow cytometry and confocal laser scanning microscopy (CLSM) revealed that the carboxylated polymers were capable of passively diffusing cell membranes and targeting mitochondria. The interplay of pendant carboxylic acids of the comb polymers and the Cy5-label was identified as major driving force for this behavior, which was demonstrated to be applicable in NIH/3T3 and N27 cell lines. Blocking of the carboxylic acids through modification with 2-methoxyethylamine and poly(2-ethyl-2-oxazoline) or replacement of the dye label with a different dye (e.g., fluorescein) resulted in an alteration of the cellular uptake mechanism toward endocytosis as demonstrated by CLSM. In contrast, partial modification of the carboxylic acid groups allowed to retain the cellular interaction, hence, rendering these comb polymers a highly functional mitochondria targeted carrier platform for future drug delivery applications and imaging purposes.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QH Natural history R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Polymerization , Copolymers , Mitochondria , Nanostructured materials -- Therapeutic use, Diagnostic imaging, Polymeric drug delivery systems | |||||||||||||||
Journal or Publication Title: | ACS Applied Materials & Interfaces | |||||||||||||||
Publisher: | American Chemical Society (ACS) | |||||||||||||||
ISSN: | 1944-8252 | |||||||||||||||
Official Date: | 28 August 2019 | |||||||||||||||
Dates: |
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Volume: | 11 | |||||||||||||||
Number: | 34 | |||||||||||||||
Page Range: | pp. 31302-31310 | |||||||||||||||
DOI: | 10.1021/acsami.9b09395 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Reuse Statement (publisher, data, author rights): | “This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/page/policy/articlesonrequest/index.html].” | |||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||
Date of first compliant deposit: | 18 October 2019 | |||||||||||||||
Date of first compliant Open Access: | 1 August 2020 | |||||||||||||||
RIOXX Funder/Project Grant: |
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