Encapsulation of a Ruthenium(II) Complex in Polylactide Nanoparticles: A Route to Remarkable Cellular Uptake for Photodynamic Therapy of Cancer

21 October 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Ruthenium complexes, and especially ruthenium(II) polypyridyl complexes, have attracted a lot of attention as potential photosensitizers for photodynamic therapy. However, some are unsuitable due to their low cellular uptake, potentially due to their relatively low degree of lipophilicity, which prevents them from penetrating tumor cells. Here, we report the conjugation of a non-cell-penetrating ruthenium polypyridyl complex, [Ru(bipy)2-dppz-7-hydroxymethyl][PF6]2 (bipy = 2,2’-bipyridine, dppz = dipyrido[3,2-a:2;2’,3’-c]phenazine) (RuOH), to a highly hydrophobic biodegradable and biocompatible polylactide to enhance its cellular uptake. The ruthenium-polylactide conjugates were prepared by drug-initiated ring-opening polymerization of lactide through the formation of a zinc alkoxide initiator and formulated into nanoparticles by nanoprecipitation. They were 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.


Photodynamic therapy
Ruthenium complexes
Drug Delivery

Supplementary materials



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