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基于稠环小分子的上转换纳米探针用于肿瘤近红外二区荧光成像引导的光热/光动力治疗。

Fused-Ring Small-Molecule-Based Bathochromic Nano-agents for Tumor NIR-II Fluorescence Imaging-Guided Photothermal/Photodynamic Therapy.

机构信息

Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, P.R. China.

Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing 210008, China.

出版信息

ACS Appl Bio Mater. 2021 Feb 15;4(2):1942-1949. doi: 10.1021/acsabm.0c01576. Epub 2021 Jan 25.

DOI:10.1021/acsabm.0c01576
PMID:35014463
Abstract

Optical imaging in the second near-infrared (NIR-II) windows reduces much more autofluorescence and photon scattering from biological tissues and allows further tissue penetration depth and superior spatial resolution in living bodies. Herein, a fused-ring 2,2'-((2Z,2'Z)-((12,13-(2-ethylhexyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2,″3″:4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]thieno[3,2-]indole-2,10-diyl)bis(methanylylidene))(5,6-difluoro-3-oxo-2,3-dihydro-1-indene-2,1-diylidene))dimalononitrile (TPBT) molecule was explored as a multifunctional tumor theranostic reagent for photothermal/photodynamic therapy guided by NIR-II imaging. The TPBT molecule has an electron-deficient core with a ladder-type multi-fused ring and shows a narrow band gap that can enhance the near-infrared absorption. The -aggregative TPBT NPs were formed by nanoprecipitation with great bathochromic shift in absorption and emission spectra, which endows them with ideal fluorescence imaging ability in the NIR-II region. Moreover, TPBT NPs present both higher photothermal conversion efficiency (∼36.5%) and effective ROS generation ability, making them excellent candidate for cancer photothermal/photodynamic therapy. Moreover, the biocompatible TPBT NPs can effectively passively target tumor sites due to their enhanced permeability and retention effect for more precision treatment. Thus, TPBT NPs as a multifunctional phototheranostic agent in the NIR-II region present promising potential in clinical cancer NIR-II imaging-guided phototherapy.

摘要

近红外二区(NIR-II)光学成像是通过减少生物组织的自发荧光和光散射,从而提高组织穿透深度和活体的空间分辨率。在此,我们探索了一种融合环 2,2'-((2Z,2'Z)-((12,13-(2-乙基己基)-3,9-二十一基-12,13-二氢-[1,2,5]噻二唑[3,4-e]噻吩[2,″3″:4',5']噻吩[2',3':4,5]吡咯[3,2-g]噻吩[2',3':4,5]噻吩[3,2-]吲哚-2,10-二基)双(亚甲基亚胺基))(5,6-二氟-3-氧代-2,3-二氢-1-茚-2,1-二亚基))二丙二腈(TPBT)分子作为一种多功能肿瘤治疗试剂,用于 NIR-II 成像引导的光热/光动力治疗。TPBT 分子具有电子缺电子核心,具有梯形多融合环,具有较窄的带隙,可增强近红外吸收。通过胶束沉淀形成的 -聚集态 TPBT NPs 在吸收和发射光谱中表现出较大的红移,赋予其在 NIR-II 区域理想的荧光成像能力。此外,TPBT NPs 具有较高的光热转换效率(约 36.5%)和有效的 ROS 生成能力,使其成为癌症光热/光动力治疗的理想候选物。此外,由于其具有增强的通透性和保留效应,生物相容性的 TPBT NPs 可以有效地被动靶向肿瘤部位,从而实现更精确的治疗。因此,NIR-II 区域的多功能光热治疗试剂 TPBT NPs 在临床癌症 NIR-II 成像引导光疗中具有广阔的应用前景。

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