A Novel Multimodal NIR-II Nanoprobe for the Detection of Metastatic Lymph Nodes and Targeting Chemo-Photothermal Therapy in Oral Squamous Cell Carcinoma
A Novel Multimodal NIR-II Nanoprobe for the Detection of Metastatic Lymph Nodes and Targeting Chemo-Photothermal Therapy in Oral Squamous Cell Carcinoma
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一种新型多模态 NIR-II 纳米探针，用于检测口腔鳞状细胞癌的转移性淋巴结和靶向化学光热治疗
DOI：
10.7150/thno.30268
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Han, Wei
中科院分区：
文献类型：
--
作者：
Wang, Yufeng;Zhang, Wansu;Han, Wei
目前口腔鳞状细胞癌（OSCC）的手术治疗必须尽可能精确，以完全切除肿瘤并保留功能组织。因此，迫切需要开发高效的荧光探针来清楚地识别肿瘤轮廓以及转移性淋巴结。化学-光热联合治疗在包括口腔鳞癌在内的多种肿瘤中的抗肿瘤作用越来越受到关注。在本研究中，我们设计了一种多模式近红外-II探针，包括光热治疗与化疗相结合，成像OSCC肿瘤和检测转移淋巴结。方法：在本研究中，我们合成了一种新的近红外（NIR）-II探针TQTPA [4，4 '-（（6，7-双（4-（己氧基）苯基）-[1，2，5]噻二唑并[3，4-g]喹喔啉-4，9-二基）双（噻吩-5，2-二基））双（N、N-二苯基苯胺）]，并制备负载TQTPA和顺式-二氯二氨合铂（CDDP）（HT@CDDP）的多峰纳米颗粒（NP）。透明质酸。在体外和体内研究了纳米颗粒的特性，包括它们的光热和成像能力。结果：纳米粒具有良好的稳定性和水溶性，对pH/透明质酸酶敏感。良好的组织穿透质量和主动靶向能力使纳米粒子能够在近红外照射下通过IR-808绘制出裸鼠原位舌肿瘤和小至1 mm的转移淋巴结的轮廓。体外和体内实验验证了纳米粒的生物相容性和低全身毒性。同时，纳米粒子作为多模式治疗剂，结合光热治疗与chemotherapy.Conclusion：具有良好的成像能力和抗肿瘤疗效，我们的纳米粒子成功地概述了原位舌肿瘤和转移性淋巴结，以及使化学光热治疗相结合。本研究为今后新的临床诊疗模式的应用奠定了坚实的基础。
Current surgical treatment for oral squamous cell carcinoma (OSCC) must be as precise as possible to fully resect tumors and preserve functional tissues. Thus, it is urgent to develop efficient fluorescent probes to clearly identify tumor delineation, as well as metastatic lymph nodes. Chemo-photothermal therapy combination attracted a growing attention to increase anti-tumor effect in various types of cancer, including OSCC. In the present study, we designed a multimodal NIR-II probe that involves combining photothermal therapy with chemotherapy, imaging OSCC tumors and detecting metastatic lymph nodes.Methods: In this study, we synthesized a novel near infrared (NIR)-II probe named TQTPA [4,4'-((6,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline-4,9-diyl)bis(thiophene-5,2-diyl))bis(N,N-diphenylaniline)] via the Suzuki reaction and prepared multimodal nanoparticles (NPs) loading TQTPA and cis-dichlorodiammine platinum (CDDP) (HT@CDDP) by hyaluronic acid. The characteristics of the NPs, including their photothermal and imaging capabilities were investigated in vitro and in vivo. Their anti-tumor efficacy was evaluated using orthotopic, tongue tumor-bearing, nude mice.Results: The NPs possessed good stability and water solubility and were pH/hyaluronidase sensitive. The good tissue penetration quality and active targeting ability enabled the NPs to draw the outline of orthotopic tongue tumors and metastatic lymph nodes as small as 1 mm in nude mice by IR-808 under NIR exposure. In vitro and in vivo experiments validated the biocompatibility and low systematic toxicity of the NPs. At the same time, the NPs acted as multimodal therapy agents, combining photothermal therapy with chemotherapy.Conclusion: With a good imaging capability and anti-tumor efficacy, our NPs successfully outlined orthotopic tongue tumors and metastatic lymph nodes as well as enabled chemo-photothermal therapy combination. Our study established a solid foundation for the application of new clinical diagnosis and treatment patterns in the future.