Tumor acidity-responsive carrier-free nanodrugs based on targeting activation via ICG-templated assembly for NIR-II imaging-guided photothermal–chemotherapy,Biomaterials Science

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Tumor acidity-responsive carrier-free nanodrugs based on targeting activation via ICG-templated assembly for NIR-II imaging-guided photothermal–chemotherapy
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-12-8 , DOI: 10.1039/d0bm01864c
Kaihang Xue _{1,

2,

3,

4,

5} , Feng Wei _{6,

7,

8,

9,

10} , Jinyan Lin _{1,

2,

3,

4,

5} , Haina Tian _{1,

2,

3,

4,

5} , Fukai Zhu _{1,

2,

3,

4,

5} , Yang Li _{8,

11,

12,

13,

14} , Zhenqing Hou _{1,

2,

3,

4,

5}

Affiliation

Carrier-free nanodrugs composed of photosensitizers and chemotherapeutic drugs show great potential in synergistic photothermal–chemotherapy. However, the targeting specificity to tumor cells is still a major obstacle for carrier-free nanodrugs. Meanwhile, almost all exogenous tumor-targeting ligands show no therapeutic effect by themselves. Here, a tumor microenvironment-driven self-targeting supramolecular nanodrug was successfully constructed via an indocyanine green (ICG)-templated small-molecule self-assembly strategy with methotrexate (MTX, folic acid-like antitumor drug) followed by post-insertion of weak acidity-responsive PEG for synergistic photothermal–chemotherapy. Interestingly, the size and morphology could be adjusted by changing the ICG-to-MTX ratio. Notably, the dynamic introduction of PEG not only could temporarily shield self-targeting function in blood to prolong the circulation time, but also could trigger the activation of self-targeting via re-exposing MTX ligands within the tumor microenvironment to enhance cellular uptake. Furthermore, the dePEGylated nanodrug would be disassembled to release MTX on-demand for chemotherapy via both stimuli of stronger lysosomal acidity and an external NIR laser. Moreover, the elimination of tumors could be realized through NIR-II fluorescence/PA imaging-guided synergistic photothermal–chemotherapy. The tumor microenvironment-driven carrier-free nanodrug based on self-targeting activation via ICG-templated assembly might provide a brand-new idea for synergistic photothermal–chemotherapy.

中文翻译：

基于ICG模板组装的靶向活化的肿瘤酸性反应性无载体纳米药物，用于NIR-II成像引导的光热化学疗法

由光敏剂和化学治疗药物组成的无载体纳米药物在协同光热化学疗法中显示出巨大潜力。但是，对肿瘤细胞的靶向特异性仍然是无载体纳米药物的主要障碍。同时，几乎所有外源性肿瘤靶向配体本身都没有显示治疗作用。在这里，肿瘤微环境驱动的自我靶向超分子纳米药物成功地通过一种以吲哚菁绿（ICG）为模板的小分子自组装策略，并使用甲氨蝶呤（MTX，叶酸样抗肿瘤药），然后将弱酸性的PEG插入后，进行协同光热化学疗法。有趣的是，可以通过更改ICG与MTX的比例来调整大小和形态。值得注意的是，动态引入PEG不仅可以暂时屏蔽血液中的自我靶向功能以延长循环时间，而且还可以通过在肿瘤微环境中重新暴露MTX配体以增强细胞摄取来触发自我靶向的激活。此外，去PEG化的纳米药物将被拆解，以通过化疗按需释放MTX强烈的溶酶体酸度刺激和外部NIR激光。此外，可以通过NIR-II荧光/ PA成像引导的协同光热化学疗法来消除肿瘤。肿瘤微环境驱动的无载体纳米药物基于通过ICG模板组装的自我靶向激活，可能为协同光热化学疗法提供崭新的思路。

更新日期：2020-12-15

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