Bright red aggregation-induced emission nanoparticles for multifunctional applications in cancer therapy.

Liping Zhang,Zhiyu Yang,Dongxia Zhu,Shi Liu,Ben Zhong Tang,Martin R Bryce,Zhigang Xie,Weilong Che,Zhongmin Su,Xingman Liu

doi:10.1039/c9sc06310b

Abstract

Developing multifunctional photosensitizers (PSs) is needed to effectively simplify cancer treatment, but it remains a big challenge. Here, two red-emitting AIE-active, donor–acceptor (D–A) PSs with small ΔEST and their AIE nanoparticles, are rationally designed and synthesized. The PS1 NPs exhibit bright red-emission with high quantum yield, appropriate 1O2 generation ability and good biocompatibility. More importantly, PS1 NPs can strongly light up the cytoplasm by gently shaking the cells for only 5 s at room temperature, indicating ultrafast staining and mild incubation conditions. In vitro and in vivo cell tracing demonstrate that PS1 NPs can track cells over 14 days, and effectively inhibit tumor growth upon irradiation. To the best of our knowledge, this work is the first example of a PS that integrates image-guided PDT, ultrafast staining and long-term tracing functions, demonstrating the “all-in-one” concept which offers great advantages for potential clinical applications.

Highlights

Image-guided photodynamic therapy (PDT) has recently gained increasing attention
PS1 NPs can strongly light up the cytoplasm by gently shaking the cells for only 5 s at room temperature, indicating ultrafast staining and mild incubation conditions
A series of AIEgen-based PSs have been reported to improve both the uorescence intensity and the 1O2 production ability in the aggregated state, due to the restriction of intramolecular motions (RIMs) which lead to energy dissipation.[46,47,48,49,50,51,52,53,54]

Summary

Introduction

PDT, (ii) ultrafast staining and (iii) long-term tracking. Is it possible to design a single “all-in-one” PS that embraces all the above functions at the same time? PSs with efficient generation of singlet oxygen (1O2) and bright red-emission are crucial to realize imaging-guided PDT.[26]. Edge Article group.[42,43,44,45] A series of AIEgen-based PSs have been reported to improve both the uorescence intensity and the 1O2 production ability in the aggregated state, due to the restriction of intramolecular motions (RIMs) which lead to energy dissipation.[46,47,48,49,50,51,52,53,54] Recently, our group obtained three red-emitting AIEgen nanoparticles (NPs) with higher brightness, enhanced 1O2 generation, and better biocompatibility compared to the pure iridium(III) complexes.[55] These precedents make AIE NPs with purely organic D–A units suitable as smart PSs to successfully obtain an “all-in-one” (image-guided PDT, ultrafast staining and long-term tracing) system In this contribution new PSs are designed and synthesized in high yield via a three-bladed propeller-like triphenylamine (TPA) as the strong donor and the dicyanovinyl (DC) groups as the acceptor, in which TPA acts as a rotor to realize AIE.[56] The two red-emitting AIE D–A and D–A–D molecules are PS1 and PS2 (Fig. 1A) and their corresponding polymer-encapsulated NPs are PS1 NPs and PS2 NPs. PS1 NPs possess bright red-emission, a large Stokes shi , appropriate 1O2 generation ability, good biocompatibility and excellent image-guided PDT activity. PS1 NPs achieve ultrafast staining of cells in only 5 s at room temperature, with excellent long-term imaging of more than 14 days in vitro and in vivo

Results and discussion

Conclusions

Ethical statement