Rational Design of Probenecid-Functionalized Silicon Phthalocyanine J-Aggregated Nanoshuttles for Lipid Droplet-Targeted Drug-Resistant Theranostics.

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yating Shen, Jingtang Wang, Congyi Peng, Guizhi Chen, Wanting Wu, Xinyi Wu, Kuizhi Chen, Kun Wang, Yiru Peng
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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.

用于脂滴靶向耐药治疗的苯丙酸功能化酞菁硅j聚集纳米穿梭体的合理设计。
Probenecid是一种通过膜蛋白调节具有潜在治疗潜力的临床尿嘧啶药物,它与哌嗪硅酞菁共价结合,构建了一种多功能治疗药物丙磺酰基哌嗪硅酞菁(PP-SiPc),用于精确光动力治疗(PDT)。通过分子间π-π堆叠、极性相互作用和疏水效应,PP-SiPc自组装成j聚集的纳米梭子(N-PP-SiPc),与自由形态的PP-SiPc相比,具有增强的UV/Vis吸收、增强的荧光和优越的光稳定性。N-PP-SiPc对脂滴(LDs)具有高特异性,能够动态跟踪和区分溶酶体和非溶酶体LDs,这是识别与非溶酶体LDs异常积累相关的药物性脂质中毒的关键能力。此外,N-PP-SiPc表现出快速的细胞内化,改善了ld的靶向性,并增强了光触发活性氧(ROS)的产生。这些特性共同促成了PDT对癌细胞和耐药菌株的有效治疗,强调了其作为能够克服耐药机制的治疗平台的潜力。这项工作为开发提供细胞器水平诊断精度的转运蛋白调节治疗纳米材料建立了蓝图。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
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.
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