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© Research
Publication :

Ruthenium-initiated polymerization of lactide: a route to remarkable cellular uptake for photodynamic therapy of cancer

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in - 30 Jan 2020

Nancy Soliman, Luke K. McKenzie, Johannes Karges, Emilie Bertrand, Mickaël Tharaud, Marta Jakubaszek, Vincent Guérineau, Bruno Goud, Marcel Hollenstein, Gilles Gasser * and Christophe M. Thomas *

Chem. Sci., 2020, 11, 2657-2663

Ruthenium complexes have attracted a lot of attention as potential photosensitizers (PSs) for photodynamic therapy (PDT). However, some of these PSs are unsuitable for PDT applications due to their low cellular uptake, which is possibly the consequence of their relatively low degree of lipophilicity, which prevents them from penetrating into tumor cells. Here, we report the simple one-pot synthesis of ruthenium-containing nanoconjugates from a non-cell-penetrating, non-phototoxic ruthenium(II) polypyridyl complex (RuOH), by a drug-initiated ring-opening polymerization of lactide through the formation of a zinc initiator. These conjugates were then formulated into nanoparticles by nanoprecipitation and characterized by means of nuclear magnetic resonance spectroscopy (NMR), matrix-assisted laser desorption/ionization – time of flight mass spectrometry (MALDI-TOF MS) and dynamic light scattering (DLS). Finally, their photo-therapeutic activity (λexc = 480 nm, 3.21 J cm−2) in cancerous human cervical carcinoma (HeLa) and non-cancerous retinal pigment epithelium (RPE-1) cells was tested alongside that of RuOH and their cellular uptake in HeLa cells was assessed by confocal microscopy and inductively coupled plasma – mass spectrometry (ICP-MS). All nanoparticles showed improved photophysical properties including luminescence and singlet oxygen generation, enhanced cellular uptake and, capitalizing on this, an improved photo-toxicity. Overall, this study demonstrates how it is possible to transform a non-phototoxic PDT PS into an active PS using an easy, versatile polymerization technique.

https://pubs.rsc.org/en/content/articlehtml/2020/sc/c9sc05976h