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In Vivo Real-Time Pharmaceutical Evaluations of Near-Infrared II Fluorescent Nanomedicine Bound Polyethylene Glycol Ligands for Tumor Photothermal Ablation.
ACS Nano ( IF 15.8 ) Pub Date : 2020-09-14 , DOI: 10.1021/acsnano.0c05885
Shengliang Li 1, 2 , Haoting Chen 1, 2 , Haile Liu 3 , Lu Liu 4 , Yuan Yuan 1, 4 , Cong Mao 1 , Wei Zhang 5 , Xiaodong Zhang 3 , Weisheng Guo 1 , Chun-Sing Lee 2 , Xing-Jie Liang 1, 4
Affiliation  

Pharmaceutical evaluations of nanomedicines are of great significance for their further launch into industry and clinic. Near-infrared (NIR) fluorescence imaging plays essential roles in preclinical drug development by providing important insights into the biodistributions of drugs in vivo with deep tissue penetration and high spatiotemporal resolution. However, NIR-II fluorescence imaging has rarely been exploited for in vivo real-time pharmaceutical evaluations of nanomedicine. Herein, we developed a highly emissive NIR-II luminophore to establish a versatile nanoplatform to noninvasively monitor the in vivo metabolism of nanomedicines bound various polyethylene glycol (PEG) ligands in a real-time manner. An alternative D–A–D conjugated oligomer (DTTB) was synthesized to achieve NIR-II emission peaked at ∼1050 nm with high fluorescence QYs of 13.4% and a large absorption coefficient. By anchoring with the DTTB molecule, intrinsically fluorescent micelles were fabricated and bound with PEG ligands at various chain lengths. In vivo NIR-II fluorescence and photoacoustic imaging results revealed that an appropriate PEG chain length could effectively contribute to the longer blood circulation and better tumor targeting. In vivo therapeutic experiments also confirmed the optimized nanomedicines have efficient photothermal elimination of tumors and good biosafety. This work offered an alternative highly fluorescent NIR-II material and demonstrated a promising approach for real-time pharmaceutical evaluation of nanomedicine in vivo.

中文翻译:

用于肿瘤光热消融的近红外II荧光纳米药物结合的聚乙二醇配体的体内实时药物评价。

纳米药物的药物评估对于将其进一步推向工业和临床领域具有重要意义。近红外(NIR)荧光成像通过深入了解具有深层组织穿透力和高时空分辨率的体内药物的生物分布,在临床前药物开发中起着至关重要的作用。然而,NIR-II荧光成像很少用于纳米药物的体内实时药物评估。在这里,我们开发了一种高发射率的NIR-II发光体,以建立通用的纳米平台来无创地监测体内纳米药物的代谢以实时方式结合各种聚乙二醇(PEG)配体。合成了另一种D–A–D共轭低聚物(DTTB),以实现在约1050 nm处达到峰值的NIR-II发射,具有13.4%的高荧光QY和大吸收系数。通过与DTTB分子锚定,制备了固有的荧光胶束,并与各种链长的PEG配体结合。体内NIR-II荧光和光声成像结果表明,适当的PEG链长可以有效促进更长的血液循环和更好的肿瘤靶向。体内治疗实验还证实优化的纳米药物具有有效的光热消除肿瘤和良好的生物安全性。这项工作提供了一种替代的高荧光NIR-II材料,并展示了一种在体内对纳米药物进行实时药物评估的有前途的方法。
更新日期:2020-10-28
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