Ayaat M. Mahmoud, Joshua P. Morrow, D. Pizzi
Jun 29, 2020
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Journal
Biomacromolecules
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 in order to provide design criteria for the manipulation of their cellular interactions. Redox-initiated RAFT polymerization of three tert-butyl protected N-acylated amino ester based acrylate monomers of different substitution and degree of polymerization (DP) yielded defined and pH-responsive carboxylic acid side chain polymers upon deprotection (N-acetyl, DP 1: P(M1); N-propionyl, DP 1: P(E1), DP 2: P(E2)). Flow cytometry studies revealed time-dependent cell association with P(E2) > P(E1) > P(M1) 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 sulfoCy5 modification caused a significant change of the cellular fate of the polymers towards lysosome trafficking. This study highlights the importance of selecting a suitable dye but also demonstrates the possibilities for the rational design of organelle-specific targeting of carboxylated polyacrylates.