主动靶向近红外二区诊疗一体化纳米颗粒用于三阴性乳腺癌的研究

引用本文: 邹志凤, 高晶, 来旖, 徐志爱. 主动靶向近红外二区诊疗一体化纳米颗粒用于三阴性乳腺癌的研究[J]. 分析化学, 2022, 50(6): 912-923. doi: 10.19756/j.issn.0253-3820.221115 shu

Citation: ZOU Zhi-Feng, GAO Jing, LAI Yi, XU Zhi-Ai. Tumor-Targeted Theranostic Probe for Near Infrared Ⅱ Window Fluorescence Imaging and Anticancer Therapy of Triple-Negative Breast Cancer[J]. Chinese Journal of Analytical Chemistry, 2022, 50(6): 912-923. doi: 10.19756/j.issn.0253-3820.221115 shu

主动靶向近红外二区诊疗一体化纳米颗粒用于三阴性乳腺癌的研究

邹志凤 ^1,2, ,
高晶 ^2, ,
来旖 ^2, ,
徐志爱 ^{1,
,}

1.
华东师范大学化学与分子工程学院, 上海 200241;
2.
中国科学院上海药物研究所, 药物研究国家重点实验室/药物研究中心, 上海 201203

通讯作者: 徐志爱,E-mail:zaxu@chem.ecnu.edu.cn

基金项目:
国家自然科学基金项目（No.22074043）资助。

摘要: 供体-受体-供体（D-A-D）型荧光探针通常具有优异的光学稳定性和生物相容性。通过分子设计，D-A-D型分子的荧光发射可以到达近红外二区（NIR-Ⅱ），同时还具有光热转换性质，因此具有生物成像和光热治疗的潜力。但是，D-A-D型分子的分子量较大，水溶性差，严重限制了其在生物诊疗领域的应用。本研究设计了具有肿瘤主动靶向性的高分子聚合物（CRGDK-PEG-b-PLGA）用于负载D-A-D型荧光探针（TQTCD），从而提高了TQTCD探针的水溶性、肿瘤特异性和光热治疗效果，并实现了诊疗一体化。CRGDK-PEG-b-PLGA与TQTCD探针在水溶液中可自组装形成均一稳定的纳米颗粒（RPP@TQTCD），并且非共价负载不影响TQTCD探针的荧光特性和光热效应。在CRGDK靶向肽的作用下，RPP@TQTCD纳米颗粒可特异性蓄积于肿瘤部位，并作用于肿瘤细胞表面高表达的神经纤毛蛋白-1（NRP-1）受体，通过受体介导的途径促进肿瘤细胞对纳米颗粒的摄取，随后在808 nm激光照射下可有效杀伤肿瘤细胞。本研究通过对疏水性探针的靶向递送，为三阴性乳腺癌（TNBC）的诊断及光热治疗提供了一种有效的策略。

关键词:

English

Tumor-Targeted Theranostic Probe for Near Infrared Ⅱ Window Fluorescence Imaging and Anticancer Therapy of Triple-Negative Breast Cancer

ZOU Zhi-Feng ^1,2, ,
GAO Jing ^2, ,
LAI Yi ^2, ,
XU Zhi-Ai ^{1,
,}

1.
School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China;
2.
State Key Laboratory of Drug Research&Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Corresponding author: XU Zhi-Ai, zaxu@chem.ecnu.edu.cn

Received Date: 08 March 2022
Revised Date: 20 April 2022
Fund Project:
Supported by the National Natural Science Foundation of China(No. 22074043).

Abstract: Donor-acceptor-donor(D-A-D) type fluorescent probes have been widely used in biological imaging due to their excellent optical stability and biocompatibility. By molecular engineering, the fluorescence emission of D-A-D type probe can shift to the near infrared Ⅱ window(NIR-Ⅱ), which shows that the probe has potential for bioimaging and photothermal therapy due to its good photothermal conversion efficiency. However, its large molecular weight leads to unavoidable disadvantages such as poor water solubility, which seriously limits its application. Therefore, in this work, an actively targeted polymer(CRGDK-PEG-b-PLGA) was designed to improve the water-solubility, tumor-specificity and photothermal efficacy of D-A-D type fluorescent probe(TQTCD), thus achieving the integration of diagnosis and treatment. CRGDK-PEG-b-PLGA and TQTCD could self-assemble to form homogeneous and stable nanoparticles(named RPP@TQTCD). This strategy did not affect the fluorescence properties and photothermal effects of TQTCD. CRGDK ligand-modification could increase the tumor accumulation of RPP@TQTCD NPs and interact with the Neuropilin-1(NRP-1) receptor, which was highly expressed on the surface of tumor cells, to promote cellular uptake of RPP@TQTCD NPs through NRP-1-CRGDK pathway.Then, RPP@TQTCD NPs could effectively kill tumor cells under 808 nm laser irradiation in vitro and in vivo. This study provided an effective strategy for the diagnosis and photothermal treatment of triple negative breast cancer(TNBC) through the targeted delivery of hydrophobic probe.

Key words:

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沈阳化工大学材料科学与工程学院沈阳 110142

主动靶向近红外二区诊疗一体化纳米颗粒用于三阴性乳腺癌的研究

通讯作者: 徐志爱,E-mail:zaxu@chem.ecnu.edu.cn

English

Tumor-Targeted Theranostic Probe for Near Infrared Ⅱ Window Fluorescence Imaging and Anticancer Therapy of Triple-Negative Breast Cancer

Corresponding author: XU Zhi-Ai, zaxu@chem.ecnu.edu.cn

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

主动靶向近红外二区诊疗一体化纳米颗粒用于三阴性乳腺癌的研究

通讯作者: 徐志爱,E-mail:zaxu@chem.ecnu.edu.cn

English

Tumor-Targeted Theranostic Probe for Near Infrared Ⅱ Window Fluorescence Imaging and Anticancer Therapy of Triple-Negative Breast Cancer

Corresponding author: XU Zhi-Ai, zaxu@chem.ecnu.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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