Highly Charged Ruthenium(II) Polypyridyl Complexes as Lysosome‐Localized Photosensitizers for Two‐Photon Photodynamic Therapy

Abstract

Photodynamic therapy( PDT) is an oninvasive medical technique that has received increasing attention over the last years and been applied for the treatment of certain types of cancer.H owever,t he currently clinically used PDT agents have several limitations,s uch as low water solubility,p oor photostability,and limited selectivity towards cancer cells,aside from having very lowt wo-photon cross-sections around 800 nm, whichl imits their potential use in TP-PDT.T o tackle these drawbacks,t hree highly positively charged ruthenium(II) polypyridyl complexes were synthesized. These complexes selectively localizei nt he lysosomes,a ni deal localization for PDT purposes.O ne of these complexes showed an impressive phototoxicity index upon irradiation at 800 nm in 3D HeLa multicellular tumor spheroids and thus holds great promise for applications in two-photon photodynamic therapy.

A Self‐Assembled Metallomacrocycle Singlet Oxygen Sensitizer for Photodynamic Therapy

“…Furthermore,a sr ecently demonstrated in an umber of studies, it is possible to construct Ru II -based systemst hat can be photoexcited within the therapeutic opticalw indow. [44][45][46][47] For example, since oligonuclearR u II complexes often display high two-photon absorption, 2PA, cross-sections, [48][49][50] using this modulara pproach, the design of macrocyclic systemsf or 2PA-PDT can be readily envisioned. Such studies will provide the basis of future publications.…”

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…In addition, several highly charged Ru(II) complexes ( 15c - 15e ), were designed as two-photon photosensitizers by the same group. 98 The three complexes were found to localize in the lysosomes via an endocytotic uptake pathway. 15c produced significant phototoxicity upon irradiation (800 nm, 10 J/cm 2 ) in 3D HeLa MCTSs, with an IC 50 value as low as 1.9 μM.…”

“…94–97 The highly positively charged Ru(II) polypyridyl complex selectively localizes in the lysosomes, and can be used in photodynamic therapy as photosensitizers (PS). 98 Moreover, lysosomes participate in an autophagic process that is linked to carcinogenesis and resistance to chemotherapy. 99 Targeting these pathways could constitute a novel approach to cancer therapy.…”

Engineering Tunable Single and Dual Optical Emission from Ru(II)–Polypyridyl Complexes through Excited State Design

“…3 These complexes possess intriguing excited state properties and are powerful structural motifs 4 in the design of advanced optical materials for dye sensitized solar cells, [5][6][7] light-emitting electrochemical cells, 8 lightemitting diodes, 9 and non-linear optics. 10 Furthermore, Ru-polypyridyl complexes have also been used as anti-tumor agents, 11,12 in artificial photosynthesis 13 and as molecular switches and machines. [14][15][16][17] The wide range of Ru-polypyridyl complexes invokes an enormous amount of fundamental and experimental studies and the interest to the optical properties of these compounds still continues to increase.…”