Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Complete list of metadatas

Cited literature [54 references]  Display  Hide  Download

https://hal-insu.archives-ouvertes.fr/hal-02465768
Contributor : Eva Fareau <>
Submitted on : Monday, April 20, 2020 - 10:46:43 AM
Last modification on : Tuesday, September 22, 2020 - 3:55:34 AM

File

c9sc05976h.pdf
Publication funded by an institution

Identifiers

Citation

Nancy Soliman, Luke Mckenzie, Johannes Karges, Emilie Bertrand, Mickaël Tharaud, et al.. Ruthenium-initiated polymerization of lactide: a route to remarkable cellular uptake for photodynamic therapy of cancer. Chemical Science , The Royal Society of Chemistry, 2020, 11 (10), pp.2657-2663. ⟨10.1039/c9sc05976h⟩. ⟨hal-02465768v2⟩

Share

Metrics

Record views

184

Files downloads

373