文献：

Dual-mode imaging guided multifunctional theranosomes with mitochondria targeting for photothermally controlled and enhanced photodynamic therapy in vitro and in vivo

文献链接：

https://pubmed.ncbi.nlm.nih.gov/29975536/

作者：

Siyu Wang, Fang Guo , Yanhui Ji , Meng Yu, Jinping Wang, Nan Li

相关产品：

磷脂-聚乙二醇2000-三苯基膦 DSPE-PEG2000-TPP

原文摘要：

Photodynamic therapy (PDT) is commonly restricted by inefficient tumor selectivity during clinical study. Hence, a mitochondria-targeting multifunctional nanocarrier "theranosome (TNS)" was developed for near-infrared fluorescent (NIRF) imaging and photoacoustic (PA) imaging. What's more, the TNS can also enhance PDT efficacy. In this work, chlorin e6 (Ce6) undertakes reactive oxygen generation and fluorescence emission. Ce6 was quenched when being encapsulated into TNS together with IR780 iodide. When exposed under 808 nm NIR light, IR780 from the TNS can be photobleached; thus, the phototoxicity of Ce6 can be activated. The IR780 induced hyperthermia damaged tumor cells to perform photothermal therapy (PTT) effect. Then lysosomes disruption under PTT facilitated PDT effect induced by Ce6 through enhanced cytoplasmic delivery. Moreover, in vitro subcellular uptake experiments showed that triphenylphosphonium (TPP) group attached to the IR780/Ce6 TNS (ICT) could promote mitochondria targeting capacity. It can lead to PDT induced oxidizing damage to the mitochondria by mitochondrial membrane potential decreasing and cell apoptosis eventually. In in vivo antitumor studies, the TPP/IR780/Ce6 TNS (TICT) substantially repressed tumor growth in nude mice. Besides, we did not find any obvious side effects to normal tissues and organs. The results suggested the TICT conjugate provided a dual NIRF/PA tumor imaging modalities with spatial resolution and superior imaging contrast. This study offered an improved phototherapy for potential theranostic application.

图为：磷脂-聚乙二醇2000-三苯基膦 DSPE-PEG2000-TPP结构式

线粒体靶向多功能纳米载体（TNS），用于近红外荧光（NIRF）成像和光声（PA）成像。其中氯化氢e6（Ce6）承担活性氧的产生和荧光发射。Ce6与IR780碘化物一起包封到TNS中时被猝灭。当暴露在808nm近红外光下时，来自TNS的IR780可以被光漂白；从而可以激活Ce6的性质。IR780诱导高温损伤的Tumor 细胞进行（PTT）效果。然后，PTT下的溶酶体破坏通过增强细胞质递送促进了Ce6诱导的PDT效应。

体外亚细胞摄取实验表明，附着在IR780/Ce6-TNS（ICT）上的三苯基鏻（TPP）基团可以提高线粒体的靶向能力。它可以通过线粒体膜电位降低导致PDT诱导的线粒体氧化损伤。TICT缀合物提供了具有空间分辨率和成像对比度的双NIRF/PA成像模式。