AIE Multinuclear Ir(III) Complexes for Biocompatible Organic Nanoparticles with Highly Enhanced Photodynamic Performance

Abstract

The singlet oxygen (¹O₂) generation ability of a photosensitizer (PS) is pivotal for photodynamic therapy (PDT). Transition metal complexes are effective PSs, owing to their high ¹O₂ generation ability. However, non-negligible cellular toxicity, poor biocompatibility, and easy aggregation in water limit their biomedical applications. In this work, a series of red-emitting aggregation-induced emission (AIE) Ir(III) complexes containing different numbers of Ir centers (mono-, di-, and trinuclear) and the corresponding nanoparticles (NPs) AIE-NPs, are designed and synthesized. The increase of ¹O₂ generation ability is in line with the increasing number of Ir centers. Compared with the pure Ir(III) complexes, the corresponding NPs offer multiple advantages: (i) brighter emission; (ii) higher phosphorescence quantum yields; (iii) longer excited lifetime; (iv) higher ¹O₂ generation ability; (v) better biocompatibility; and (vi) superior cellular uptake. Both in vitro and in vivo experiments corroborate that AIE-NPs with three iridium centers possess potent cytotoxicity toward cancer cells and effective inhibition of tumor growth. To the best of knowledge, this work is the first example of NPs of multinuclear AIE Ir(III) complexes as PSs for enhanced PDT. This study offers a new method to improve the efficiency of PSs for clinical cancer treatments.

Keywords: aggregation‐induced emission; in vivo; multinuclear Ir(III) complexes; nanoparticles; photodynamic therapy.

Figure 1

A) Chemical structures of PS1, PS2, and PS3; B) The synthesis of NPs; C) Schematic illustration of PS3 NPs as PSs for PDT.

Figure 2

A) UV–vis absorption spectra and emission spectra of PS1 in THF, THF/water (v:v) = 2/3, and PS1 NPs in water (λ_ex = 469 nm), inset: emission images of the PS1 and PS1 NPs under 365 nm UV illumination; B) UV–vis absorption spectra and emission spectra of PS2 in THF, THF/water (v:v) = 1/4, and PS2 NPs in water (λ_ex = 469 nm), inset: emission images of the PS2 and PS2 NPs under 365 nm UV illumination; C) UV–vis absorption spectra and emission spectra of PS3 in THF, THF/water (v:v) = 2/3, and PS3 NPs in water (λ_ex = 469 nm), inset: emission images of the PS3 and PS3 NPs under 365 nm UV illumination; D) Comparison of the decay rates of different PSs under irradiation (450 nm, 20 mW cm⁻²), A ₀ = absorption of ICG without irradiation. A = real‐time absorption of ICG with different irradiation time; E) Time‐dependent ¹O₂ generation kinetics. A ₀ = absorption of ICG without irradiation. A = real‐time absorption of ICG with different irradiation time; F) Stability of size distribution of changes of different PSs during 14 d, inset: the TEM images of (a) PS1 NPs, (b) PS2 NPs, and (c) PS3 NPs. (PS1 or PS2 or PS3 or PS1 NPs or PS2 NPs or PS3 NPs) = 10⁻⁵ m, (ICG) = 6.5 × 10⁻⁶ m.

Figure 3

Cell viability of different PSs against HeLa cells A,C) under dark and B,D) under light (450 nm, 20 mW cm⁻², 30 min); E) CLSM images of HeLa cells incubated with PS3 and PS3 NPs (20 µg mL⁻¹) for 6 h, the scale bars are 20 µm; F) Generation of intracellular ROS mediated by PS3 and PS3 NPs upon irradiation (450 nm, 20 mW cm⁻², 20 min) as indicated by the fluorescence of DCF.

Figure 4

A) Representative images of mice. The hair on the thigh was removed immediately before irradiation. The images were taken on day 14 after irradiation and the different hair length on the different mice is due to an inconsistent rate of hair growth. B) Harvested tumors from various groups treated (a) with saline, (b) with saline and light, (c) with PS3 NPs, (d) with PS3 NPs and light (100 mg mL⁻¹, 100 µL), light irradiation (450 nm, 200 mW cm⁻², 20 min). C) Tumor volume measurement for different groups of mice (****, P < 0.0001, n = 5 per group, PDT vs other groups). D) Body weights of mice for different groups of mice.