Localization matters: a nuclear targeting two-photon absorption iridium complex in photodynamic therapy

Abstract

We present a two-photon (2P, 800 nm) PDT cyclometalated Iridium(iii) complex (Ir-Es) that targets the intracellular nucleus. The complex is capable of migrating sequentially from the nucleus to mitochondria and inducing dual-damage under light exposure. This study suggests that with minor modification of the terminal moieties of complexes, their final intracellular destinations and PDT efficiency can be significantly impacted.

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

“…Over the measured range, the maximum TPA cross sections δ max of 1 a – 3 a and 1 b – 3 b ranged from 38 to 129 GM (1 GM=10 −50 cm 4 photon −1 ) at λ =740 nm (Figure S14 and Table S3 of the Supporting Information). These values are moderate compared with those of other Ir III complexes measured by the same method ,. From the log–log plot of the emission intensity against incident power, the linear regression slopes of 1 a – 3 a and 1 b – 3 b are 1.98±0.01, 2.00±0.03, 2.05±0.01, 1.95±0.02, 2.05±0.01 and 1.94±0.01, respectively, which indicate nonlinear TPA of the Ir III complexes (Figure S15 of the Supporting Information).…”

Photosensitizers for Two‐Photon Excited Photodynamic Therapy

“…Recently, Tian et al reported a series of terpyridine‐based cyclometalated iridium (III) complexes ( 27 – 31 , shown in Figure ). To adjust the pull/push electronic capability and bioaffinity of 27 – 31 , five different terminal substituents were attached onto the terpyridine ligand.…”

“…Compared with conjugated porphyrin derivatives, the water solubility and lipid–water partition ratio of polypyridyl metal complexes are easier to be modulated to achieve a high cellular uptake. However, the σ 2 values of most reported polypyridyl metal complexes are relatively low, which will limit their potentials on 2PE‐PDT. Additionally, though it is beneficial to kill tumor cells when a polypyridyl metal complex can target cell nucleus, induce DNA binding and cleavage (such as 27 ), it is also dangerous if any genetic mutation takes place in normal cells during the PDT process.…”

Recent Advances in the Design of Targeted Iridium(III) Photosensitizers for Photodynamic Therapy

“…Recently, Tian et al. reported complex 79 (Scheme ) as a nucleus‐targeted PS for two‐photon PDT (800 nm) . Complexes 79 – 83 have high two‐photon absorption cross‐sections at 800 nm with σ 2 values ranging from 60 to 110 GM.…”