Engineering AIEgens-Tethered Gold Nanoparticles with Enzymatic Dual Self-Assembly for Amplified Cancer-Specific Phototheranostics

• Published in: ACS nano Vol. 18; no. 39; pp. 26784 - 26798
• Main Authors: Bian, Jiayi, Xu, Yingjie, Sun, Minghao, Ma, Zerui, Li, Hao, Sun, Changrui, Xiong, Fei, Zhao, Xiaopeng, Yao, Wenjing, Chen, Yue, Ma, Yuanyuan, Yao, Xikuang, Ju, Shenghong, Fan, Wenpei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.10.2024
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Gold - chemistry; Humans; Metal Nanoparticles - chemistry; Mice; Optical Imaging; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Photoacoustic Techniques; Phototherapy; Photothermal Therapy; Theranostic Nanomedicine; self-assembly; AIE luminogens; gold nanoparticles; enzymatic responsiveness; cancer phototheranostics
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/acsnano.4c07403

Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.