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A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting

Acosta-Gutiérrez, Silvia; Matias, Diana; Avila-Olias, Milagros; Gouveia, Virginia M; Scarpa, Edoardo; Forth, Joe; Contini, Claudia; ... Battaglia, Giuseppe; + view all (2022) A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting. ACS Central Science 10.1021/acscentsci.2c00146. (In press). Green open access

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Abstract

Phenotypic targeting requires the ability of the drug delivery system to discriminate over cell populations expressing a particular receptor combination. Such selectivity control can be achieved using multiplexed-multivalent carriers often decorated with multiple ligands. Here, we demonstrate that the promiscuity of a single ligand can be leveraged to create multiplexed-multivalent carriers achieving phenotypic targeting. We show how the cellular uptake of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacry-late) (PMPC-PDPA) polymersomes varies depending on the receptor expression among different cells. We investigate the PMPC–PDPA polymersome insertion at the single chain/receptor level using all-atom molecular modeling. We propose a theoretical statistical mechanics-based model for polymersome–cell association that explicitly considers the interaction of the polymersome with the cell glycocalyx shedding light on its effect on the polymersome binding. We validate our model experimentally and show that the binding energy is a nonlinear function, allowing us to tune the interaction by varying the radius and degree of polymerization. Finally, we show that PMPC–PDPA polymersomes can be used to target monocytes in vivo due to their promiscuous interaction with SRB1, CD36, and CD81.

Type: Article
Title: A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acscentsci.2c00146
Publisher version: https://doi.org/10.1021/acscentsci.2c00146
Language: English
Additional information: This work is licensed under an Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10147345
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