Abstract Nanocarriers have provided a new platform for the selective delivery of therapeutic agents into targeted cells and tissues using safe, efficient, and tractable routes. In particular, the integration of multiple therapeutic/diagnostic modalities into a single system has the great potential of enhancing theranostic efficiency against serious diseases with reduced side effects. In this study, a new light-triggered theranostic system using photosensitizer-conjugated gold nanorods (AuNR) with glutathione (GSH)-sensitive linkages was developed for cancer imaging and combinational phototherapy of photodynamic therapy (PDT) and photothermal therapy (PTT) to achieve a synergistic cancer treatment. AuNRs with various aspect ratios were prepared as photothermal agents, and then a folic acid (FA)-PEG block copolymer (FAP) and pheophorbide a (Pheo) were chemically conjugated to the surface of AuNRs for active tumor targeting and PDT, respectively. The configuration of Pheo-conjugated AuNR nanocarriers has been precisely controlled through adjusting the feed composition ratio and the relationship between aspect ratio and absorption band of AuNRs. In particular, an AuNR with an aspect ratio of 3.84 and longitudinal plasmon resonance at 873 nm (Pheo-conjugated AuNR100) exhibited superior performance in singlet oxygen generation, photothermal conversion effect, and GSH-mediated selective release of Pheo. Moreover, it also showed tumor targeting activity and a PDT-PTT synergistic effect. These results indicate that this multifunctional AuNR system with tumor targeting ability and GSH-sensitive linkages would be highly efficient for noninvasive cancer treatment by integrating cancer imaging diagnostics and synergistic therapy.

中文翻译：

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基于谷胱甘肽反应性脱镁叶绿素 a 偶联金纳米棒配方的光热增强光动力疗法用于癌症治疗诊断

摘要 纳米载体为使用安全、高效和易处理的途径将治疗剂选择性递送到靶细胞和组织中提供了一个新平台。特别是，将多种治疗/诊断方式集成到一个系统中具有提高治疗诊断效率以减少副作用的严重疾病的巨大潜力。在这项研究中，使用带有谷胱甘肽 (GSH) 敏感键的光敏剂偶联金纳米棒 (AuNR) 开发了一种新的光触发治疗诊断系统，用于癌症成像和光动力疗法 (PDT) 和光热疗法 (PTT) 的组合光疗，以实现一种协同的癌症治疗。制备了各种纵横比的 AuNRs 作为光热剂，然后将叶酸 (FA)-PEG 嵌段共聚物 (FAP) 和脱镁叶绿素 a (Pheo) 化学偶联到 AuNRs 的表面，分别用于主动肿瘤靶向和 PDT。Pheo-共轭AuNR纳米载体的构型通过调整进料组成比和AuNRs的纵横比与吸收带的关系得到精确控制。特别是，纵横比为 3.84 和纵向等离子体共振在 873 nm 的 AuNR（Pheo-共轭 AuNR100）在单线态氧产生、光热转换效应和 GSH 介导的 Pheo 选择性释放方面表现出优异的性能。此外，它还显示出肿瘤靶向活性和 PDT-PTT 协同作用。