Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy

Minglun Liu, Yuncong Chen (), Yan Guo, Hao Yuan, Tongxiao Cui, Shankun Yao, Suxing Jin, Huanhuan Fan, Chengjun Wang, Ran Xie, Weijiang He () and Zijian Guo ()
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Minglun Liu: Nanjing University
Yuncong Chen: Nanjing University
Yan Guo: Nanjing University
Hao Yuan: Nanjing University
Tongxiao Cui: Nanjing University
Shankun Yao: Nanjing University
Suxing Jin: Nanjing University
Huanhuan Fan: Nanjing University
Chengjun Wang: Sinopec Shengli Petroleum Engineering Limited Company
Ran Xie: Nanjing University
Weijiang He: Nanjing University
Zijian Guo: Nanjing University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Golgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to the lack of effective design strategy, photosensitizers (PSs) with specific GA targeting ability are in high demand and yet quite challenging. Herein, we report an aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target the GA via caveolin/raft mediated endocytosis with a Pearson correlation coefficient up to 0.98. Additionally, the introduction of pyrene into TPE-PyT-CPS can reduce the energy gap between the lowest singlet state (S1) and the lowest triplet state (T1) (ΔEST) and exhibits enhanced singlet oxygen generation capability. GA fragmentation and cleavage of GA proteins (p115/GM130) are observed upon light irradiation. Meanwhile, the apoptotic pathway is activated through a crosstalk between GA oxidative stress and mitochondria in HeLa cells. More importantly, GA targeting TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS generation rate. This work provides a strategy for the development of PSs with specific GA targeting ability, which is of great importance for precise and effective PDT.

Date: 2022
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DOI: 10.1038/s41467-022-29872-7

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