Ruthenium-initiated polymerization of lactide: a route to remarkable cellular uptake for photodynamic therapy of cancer - Archive ouverte HAL Access content directly
Journal Articles Chemical Science Year : 2020

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

(1) , (2, 3) , (1) , (3) , (4) , (1, 5) , (6) , (7) , (2) , (1) , (1)
1
2
3
4
5
6
7

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.
Fichier principal
Vignette du fichier
c9sc05976h.pdf (673.23 Ko) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

hal-02465768 , version 1 (04-02-2020)
hal-02465768 , version 2 (20-04-2020)

Identifiers

Cite

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, 2020, 11 (10), pp.2657-2663. ⟨10.1039/c9sc05976h⟩. ⟨hal-02465768v2⟩
109 View
152 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More