Integrating Anion−π<sup>+</sup> Interaction and Crowded Conformation to Develop Multifunctional NIR AIEgen for Effective Tumor Theranostics via Hippo–YAP Pathway
Shiping Yang, Hongchi Yu, Junkai Liu, Lunjie Ma, Zhe Hou, Jia Ma, Michael Z. Miao, Ryan T. K. Kwok, Jianwei Sun, Herman H. Y. Sung, Ian D. Williams, Jacky W. Y. Lam, Xiaoheng Liu, Ben Zhong Tang
Abstract
The technology of aggregation-induced emission (AIE) presents a promising avenue for fluorescence imaging-guided photodynamic cancer therapy. However, existing near-infrared AIE photosensitizers (PSs) frequently encounter limitations, including tedious synthesis, poor tumor retention, and a limited understanding of the underlying molecular biology mechanism. Herein, an effective molecular design paradigm of anion−π + interaction combined with the inherently crowded conformation that could enhance fluorescence efficacy and reactive oxygen species generation was proposed through a concise synthetic method. Mechanistically, upon photosensitization, the Hippo signaling pathway contributes to the death of melanoma cells and promotes the nuclear location of its downstream factor, yes-associated protein, which regulates the transcription and expression of apoptosis-related genes. The finding in this study would trigger the development of high-performance and versatile AIE PSs for precision cancer therapy based on a definite regulatory mechanism.