{"title":"Rational Design of Probenecid-Functionalized Silicon Phthalocyanine J-Aggregated Nanoshuttles for Lipid Droplet-Targeted Drug-Resistant Theranostics.","authors":"Yating Shen, Jingtang Wang, Congyi Peng, Guizhi Chen, Wanting Wu, Xinyi Wu, Kuizhi Chen, Kun Wang, Yiru Peng","doi":"10.1002/adhm.202502542","DOIUrl":null,"url":null,"abstract":"<p><p>Probenecid, a clinical uricosuric agent with emerging therapeutic potential via membrane protein modulation, is covalently integrated with piperazine silicon phthalocyanine to construct a multifunctional theranostics, propanesulfonylpiperazine silicon phthalocyanine (PP-SiPc), for precise photodynamic therapy (PDT). Through intermolecular π-π stacking, polar interactions, and hydrophobic effects, PP-SiPc self-assembled into J-aggregated nanoshuttles (N-PP-SiPc) that exhibit enhanced UV/Vis absorption, intensified fluorescence, and superior photostability compared to the free form of PP-SiPc. N-PP-SiPc demonstrates high specificity for lipid droplets (LDs), enabling dynamic tracking and discrimination between lysosomal and non-lysosomal LDs-a critical capability for identifying drug-induced lipidosis associated with abnormal accumulation of non-lysosomal LDs. Furthermore, N-PP-SiPc exhibits rapid cellular internalization, improved targeting of LDs, and enhanced light-triggered reactive oxygen species (ROS) generation. These properties collectively contributed to potent PDT efficacy against both cancer cells and drug-resistant strains, underscoring its potential as a theranostic platform capable of overcoming resistance mechanisms. This work establishes a blueprint for developing transporter-modulated theranostic nanomaterials offering organelle-level diagnostic precision.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02542"},"PeriodicalIF":9.6000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Healthcare Materials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1002/adhm.202502542","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Probenecid, a clinical uricosuric agent with emerging therapeutic potential via membrane protein modulation, is covalently integrated with piperazine silicon phthalocyanine to construct a multifunctional theranostics, propanesulfonylpiperazine silicon phthalocyanine (PP-SiPc), for precise photodynamic therapy (PDT). Through intermolecular π-π stacking, polar interactions, and hydrophobic effects, PP-SiPc self-assembled into J-aggregated nanoshuttles (N-PP-SiPc) that exhibit enhanced UV/Vis absorption, intensified fluorescence, and superior photostability compared to the free form of PP-SiPc. N-PP-SiPc demonstrates high specificity for lipid droplets (LDs), enabling dynamic tracking and discrimination between lysosomal and non-lysosomal LDs-a critical capability for identifying drug-induced lipidosis associated with abnormal accumulation of non-lysosomal LDs. Furthermore, N-PP-SiPc exhibits rapid cellular internalization, improved targeting of LDs, and enhanced light-triggered reactive oxygen species (ROS) generation. These properties collectively contributed to potent PDT efficacy against both cancer cells and drug-resistant strains, underscoring its potential as a theranostic platform capable of overcoming resistance mechanisms. This work establishes a blueprint for developing transporter-modulated theranostic nanomaterials offering organelle-level diagnostic precision.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.