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.

Highlights

  • Photodynamic therapy (PDT) has attracted great attention in recent years due to the noninvasive nature, high specificity, controllability, and insignificant side effects compared with traditional surgery, chemotherapy, and radiotherapy.[1]

  • The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) distributions of PS1, PS2, and PS3 are shown in Figure S22 (Supporting Information)

  • We have established for the first time that the efficiency of photodynamic therapy (PDT) can be enhanced by increasing the number of metal centers in PSs

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Summary

Introduction

Photodynamic therapy (PDT) has attracted great attention in recent years due to the noninvasive nature, high specificity, controllability, and insignificant side effects compared with traditional surgery, chemotherapy, and radiotherapy.[1]. An effective method for improving the efficiency of singlet oxygen generation is to accelerate the intersystem crossing (ISC) by introducing heavy atoms into PSs, such as halogens, transition metals, etc.[7] Especially, Ir(III) complexes have attracted considerable attention as PSs because of their ideal photophysical properties, large Stokes shift, and high ISC ability.[8] For example, Huang and co-workers designed a mitochondria-targeted Ir(III) complex as a PS to improve PDT effects under hypoxia.[9] An ingenious organoiridium PS that can induce specific oxidative attack on proteins within cancer cells was constructed by Sadler and co-workers.[10] The previous reports mainly focused on mononuclear Ir(III) complexes, whereas research into multinuclear Ir(III) complexes as PSs has been overlooked. Is it possible to combine the advantages of multinuclear transition metal complexes and NPs simultaneously to enhance the PDT effect? Inspired by this idea, we synthesized a series of red-emitting AIE Ir(III) complexes and their corresponding NPs and explored their potential as PSs for clinical cancer treatments

Results and Discussion
Conclusions
Conflict of Interest

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