Peptide Supramolecular Assembly‐Instructed In Situ Self‐Aggregation for Stratified Targeting Sonodynamic Therapy Enhancement of AIE Luminogens. Issue 4 (9th December 2022)

• Record Type: Journal Article
• Authors: Jiang, Weixi; Cheng, Chen; Qiu, Xiaoling; Chen, Li; Guo, Xun; Luo, Yuanli; Wang, Jingxue; Wang, Junrui; Xie, Zhuoyan; Li, Pan; Wang, Zhigang; Ran, Haitao; Zhou, Zhiyi; Ren, Jianli
• Is Part Of: Advanced science. Volume 10:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-09
• Subjects: aggregation‐induced emission -- in situ self‐aggregation -- peptide‐based supramolecular self‐assembly -- sonodynamic therapy -- stratified targeting; Science -- Periodicals; 505
• DOI: 10.1002/advs.202204989
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The emergence of aggregation‐induced emission luminogens (AIEgens) has attracted substantial scientific attention. However, their antitumor efficacy in photodynamic therapy (PDT) is significantly restricted by the poor water solubility and limited treatment depth. Therefore, a novel AIEgens‐involved therapeutic platform with good permeability and bioavailability is urgently required. Herein, supramolecular chemistry is combined with the AIEgen bis‐pyrene (BP) to construct a peptide–AIEgen hybrid nanosystem (PAHN). After intravenous injection, the versatile nanoplatform not only improved the hydrophilicity of BP but also achieved stratified targeting from tumor to mitochondrial and induced mitochondrial dysfunction, thus activating caspase‐3 upregulation. Then, sonodynamic therapy (SDT), an alternative modality with high tissue penetrability, is performed to evoke reactive oxygen species (ROS) generation for BP. More importantly, since the hydrophilic shell is separated from the nanosystem by the specific cleavage of caspase‐3, the resulting decrease in hydrophilicity induced tight self‐aggregation of PAHN residues in situ, further allowing more absorbed energy to be used for ROS generation under ultrasound irradiation and enhancing SDT efficacy. Moreover, severe oxidative stress resulting from ROS imbalance in the mitochondria initiates the immunogenic cell death process, thus evoking antitumor immunogenicity. This PAHN provides prospective ideas into AIE‐involved antitumor therapy and design of peptide‐AIEgens hybrids. Abstract : Inspired by the characteristics of aggregation‐induced emission luminogens (AIEgens), a peptide‐AIEgen hybrid nanosystem (PAHN) with a unique strategy of "stratified targeting" and "in situ self‐aggregation" is designed for synergistic enhanced sonodynamic therapy (SDT). The specific cleavage of caspase‐3 induces tight self‐aggregation of PAHN, further allowing more absorbed energy used for reactive oxygen species generation and enhancing mitochondria‐mediated oxidative stress.