Tuning Cellular Interactions of Carboxylic Acid-Side-Chain-Containing Polyacrylates: The Role of Cyanine Dye Label and Side-Chain Type
- 1 August 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 21 (8), 3007-3016
- https://doi.org/10.1021/acs.biomac.0c00244
Abstract
Cellular uptake and intracellular targeting to specific organelles are key events in the cellular processing of nanomaterials. Herein, we perform a detailed structure-property relationship study on carboxylic acid-side-chain-bearing polyacrylates to provide design criteria for the manipulation of their cellular interactions. Redox-initiated reversible addition-fragmentation chain-transfer (RRAFT) polymerization of three tert-butyl-protected N-acylated amino ester-based acrylate monomers of different substitutions and degrees of polymerization (DPs) yielded defined and pH-responsive carboxylic acid-side-chain polymers upon deprotection (N-acetyl, DP 1: P(M-1);N-propionyl, DP 1: P(E-1), DP 2: P(E-2)). Flow cytometry studies revealed time-dependent cell association with P(E-2) > P(E-1) > P(M-1) at any given time point. Importantly, the type of cyanine dye used for labeling was found to significantly influence the cellular processing of the polymers. Changing the dye from Cy5 to its sulfonated version sulfoCy5 resulted in a much lower cellular association. Moreover, Cy5-labeled polymers were targeted to mitochondria, while sulfoCyS modification caused a significant change in the cellular fate of polymers toward lysosome trafficking. This study highlights the importance of selecting a suitable dye but also demonstrates the possibilities for the rational design of organellespecific targeting of carboxylated polyacrylates.Funding Information
- Monash University
- National Health and Medical Research Council (APP1109945)
- Australian Research Council (CE140100036)
This publication has 49 references indexed in Scilit:
- Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapyEuropean Journal of Pharmaceutics and Biopharmaceutics, 2015
- Physicochemical Properties Determine Nanomaterial Cellular Uptake, Transport, and FateAccounts of Chemical Research, 2012
- Water-Soluble Conjugated Polymers for Imaging, Diagnosis, and TherapyChemical Reviews, 2012
- Biodegradable synthetic polymers: Preparation, functionalization and biomedical applicationProgress in Polymer Science, 2012
- Nanoparticles for intracellular-targeted drug deliveryNanotechnology, 2011
- Polymers for Drug Delivery SystemsAnnual Review of Chemical and Biomolecular Engineering, 2010
- Ligands for Clathrin-Mediated Endocytosis Are Differentially Sorted into Distinct Populations of Early EndosomesCell, 2006
- Design and development of polymers for gene deliveryNature Reviews Drug Discovery, 2005
- Dendritic Polymers in Biomedical Applications: From Potential to Clinical Use in Diagnostics and TherapyAngewandte Chemie, 2002
- Applications of thermally reversible polymers and hydrogels in therapeutics and diagnosticsJournal of Controlled Release, 1987