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一种新型的多模态近红外二区纳米探针,用于检测口腔鳞状细胞癌的转移性淋巴结,并进行靶向化疗-光热治疗。

A Novel Multimodal NIR-II Nanoprobe for the Detection of Metastatic Lymph Nodes and Targeting Chemo-Photothermal Therapy in Oral Squamous Cell Carcinoma.

机构信息

Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing 210008, China.

Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 22 Hankou Road, Nanjing 210093, China.

出版信息

Theranostics. 2019 Jan 1;9(2):391-404. doi: 10.7150/thno.30268. eCollection 2019.

Abstract

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. : 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 -dichlorodiammine platinum (CDDP) (HT@CDDP) by hyaluronic acid. The characteristics of the NPs, including their photothermal and imaging capabilities were investigated and . Their anti-tumor efficacy was evaluated using orthotopic, tongue tumor-bearing, nude mice. : 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. and 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. : 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.

摘要

目前,口腔鳞状细胞癌(OSCC)的外科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,迫切需要开发有效的荧光探针来清楚地识别肿瘤边界以及转移性淋巴结。化学-光热联合治疗引起了越来越多的关注,以提高各种类型癌症(包括 OSCC)的抗肿瘤效果。在本研究中,我们设计了一种多模式近红外二区(NIR-II)探针,该探针结合了光热治疗和化疗,用于成像 OSCC 肿瘤和检测转移性淋巴结。

在这项研究中,我们通过 Suzuki 反应合成了一种新型近红外(NIR)-II 探针,命名为 TQTPA[4,4'-((6,7-双(4-(己氧基)苯基)[1,2,5]噻二唑[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)],并通过透明质酸制备了装载 TQTPA 和 -二氯二氨合铂(CDDP)(HT@CDDP)的多模式纳米粒子(NPs)。研究了 NPs 的特性,包括光热和成像能力。通过原位、舌肿瘤荷瘤、裸鼠评估了它们的抗肿瘤功效。

NPs 具有良好的稳定性和水溶性,并且对 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 NPs 能够在 NIR 照射下通过 IR-808 在裸鼠中勾勒出小至 1mm 的原位舌肿瘤和转移性淋巴结的轮廓。体外和体内实验验证了 NPs 的生物相容性和低系统毒性。同时,NPs 作为多模式治疗剂,结合光热治疗和化疗。

我们的 NPs 具有良好的成像能力和抗肿瘤功效,成功地勾勒出了原位舌肿瘤和转移性淋巴结,并实现了化学-光热联合治疗。我们的研究为未来新的临床诊断和治疗模式的应用奠定了坚实的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d78c/6376191/ae2e3b060a77/thnov09p0391g001.jpg

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