Complete pathway elucidation and heterologous reconstitution of (+)-nootkatone biosynthesis from Alpinia oxyphylla

Xiaomin Deng, Ziling Ye, Jingyu Duan, Fangfang Chen, Yao Zhi, Man Huang, Minjian Huang, Weijia Cheng, Yujie Dou, Zhaolin Kuang, Yanglei Huang, Guangkai Bian, Zixin Deng, Tiangang Liu, Li Lu

New Phytologist 2023

https://nph.onlinelibrary.wiley.com/share/6ZCY8V5GM5F8T7ZADUCR?target=10.1111/nph.19375

Abstract

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) can significantly enhance antitumor efficacy via a synergistic therapeutic effect. However, developing a controllable and effective strategy for combined phototherapy remains a challenge. Herein, an intelligent photoactive agent based on supramolecular nanovesicles is presented, with a capacity of glutathione-responsive transformation from PTT to PDT to achieve controllable phototherapy. When linked by cystamine, the self-assembling nature of hydrophobic corrole molecules and hydrophilic PEG5000 chains induces the formation of supramolecular nanovesicles, which exhibit a high photothermal conversion efficiency of 55.1% due to the strong π-stacking of photosensitizing corrole molecules, while the fluorescence and photodynamic effect are inhibited. Interestingly, upon exposure to glutathione, the disulfide bonds of cystamine would gradually dissociate, resulting in the disassembly of nanovesicles into discrete corrole molecules and the concomitant recovery of photodynamic ability. In vitro and in vivo studies demonstrated that the tumor-responsive structural change of supramolecular nanovesicles and PTT-to-PDT transformation were crucial for optimized antitumor outcomes, allowing PTT, combined PTT/PDT, and PDT at different time points after one injection. Our work manifested that supramolecular photoactive nanovesicles could be rationally designed to realize controllable phototherapy, providing a unique strategy for constructing intelligent nanomedicine.