Mitochondria‐Targeting Phototheranostics by Aggregation‐Induced NIR‐II Emission Luminogens: Modulating Intramolecular Motion by Electron Acceptor Engineering for Multi‐Modal Synergistic Therapy

Abstract

Phototheranostic agents have thrived as promising tools for cancer theranostics because of the integration of sensitive in situ fluorescence imaging and effective multi‐model synergistic therapy. However, how to manipulate the intangible photon energy transfer to balance the competitive radiative and nonradiative processes is still challenging. Although numerous phototheranostic molecules are reported, their complicated molecular design and tedious synthesis often stumble further their development. Herein, three simple molecules with electron donating−accepting structures are developed. The electron acceptor engineering on molecules by introducing acridinium unit gives rise to TPEDCAc with aggregation‐induced second near‐infrared emission (AIE NIR‐II), high reactive oxygen species generation capability, and excellent photothermal conversion efficiency (44.8%) due to the drastic intramolecular motion of large acridinium rotor and balanced AIE effect. Experimental analysis and calculation on the controlled molecules suggested that large torsional angle and the strong electron‐withdrawing ability of the acridinium unit are keys for NIR‐II emission and balanced photodynamic/photothermal conversion. Impressively, the positively charged TPEDCAc shows mitochondria‐targeting capability and high performance in in vivo multi‐modal cancer theranostics under NIR laser irradiation. Hence, this work not only provides a single NIR‐II AIE‐based multi‐modal cancer theranostic system but inspires new insights into future development of new theranostic platforms.

Single-molecule photosensitizers for NIR-II fluorescence and photoacoustic imaging guided precise anticancer phototherapy

“…This result also explains why the PCE of CyQN-BTT was the highest among the three sm-PSs. Thus, the high-performance phototherapy properties of CyQN-BTT could be attributed to several factors: (i) the strong D–A relationship reduced HOMO–LUMO energy levels and promoted the ISC efficiency; 33–35,39 (ii) the twisted conformation provided some space for the active rotor motion to enhance the PCE; 31,35,36 and (iii) the twisted conformation enhanced TICT feature. 31,32,35…”

Cu-Hemin Nanosheets and Indocyanine Green Co-Loaded Hydrogel for Photothermal Therapy and Amplified Photodynamic Therapy

“…The good antitumor effect of PDT mainly comes from the direct cytotoxic effect on tumor cells and the indirect destruction of TME to regulate cell death (38)(39)(40)(41). A large amount of ROS is generated during the PDT process (42).…”

Organic conjugated small molecules with donor–acceptor structures: design and application in the phototherapy of tumors

“…, 2,3,3-trimethylindolenine, quinolinium and acridinium) were also used as A units to construct anion–π + AIEgens. 103,104 Among the ions of pyridinium, quinolinium and acridinium, the acridinium ion has the highest electron-withdrawing ability. So TPEDCAc using the acridinium ion as the A unit showed the broadest absorption and the strongest ICT intensity, which give TPEDCAc the highest PDT activity.…”

“…So TPEDCAc using the acridinium ion as the A unit showed the broadest absorption and the strongest ICT intensity, which give TPEDCAc the highest PDT activity. 104 Moreover, compared with TPEDCPy and TPEDCQY, TPEDCAc showed obvious PTT activity due to skeleton distortion and rotor twisting (Table 1). Based on the photophysical features of these photosensitizers, their therapeutic effects were tested in MCF7 tumor-bearing nude mice.…”