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新型小分子载染料脂质纳米颗粒,具有高效近红外-II 吸收,用于肝癌的光声成像和光热治疗。

Novel small molecular dye-loaded lipid nanoparticles with efficient near-infrared-II absorption for photoacoustic imaging and photothermal therapy of hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, PR China.

Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

出版信息

Biomater Sci. 2019 Aug 1;7(8):3165-3177. doi: 10.1039/c9bm00528e. Epub 2019 May 24.

DOI:10.1039/c9bm00528e
PMID:31123730
Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is the second leading cause of mortality in cancer patients. Thus, accurate diagnosis and effective treatment of the malignancy is very critical for HCC patients. The photoacoustic (PA) nanoparticle with ultra-sensitive imaging signals and high photothermal conversion efficacy is a new and promising method for achieving the desired goals. In this study, we have synthesized a novel lipid nanoparticle based on IR-1061 dyes by encapsulating the dye into a liposome which was modified by DSPE-PEG. We conducted serial experiments to investigate the PA diagnosis performance, the surgical navigation, and the photothermal therapy (PTT) capability of the novel nanoparticle (Polipo-IR NP) in nude mice bearing HCC. The results showed that our novel nanoparticles exhibited strong laser energy absorption at 1064 nm wavelength, high photothermal conversion efficacy (45.25%) and ultra-sensitive PA signals. The in vivo PA studies demonstrated that the proposed nanoparticles could diagnose tumors non-invasively and accurately with a strong signal-to-noise ratio of 5.98 ± 0.23 at 3 h post-injection and could successfully achieve radical resection of tumors intraoperatively. Furthermore, the PTT test demonstrated a remarkable cancer cell killing ability because of its high photothermal conversion efficacy. The excellent photostability and high biocompatibility were also validated by in vitro and in vivo experiments. Thus, our proposed NIR-II PA and PTT nanoparticles based on the IR-1061 dye would potentially provide novel insights into understanding polymethine dyes in nanomedicine and would greatly benefit early diagnosis and treatment of HCC patients.

摘要

肝细胞癌(HCC)是全球最常见的恶性肿瘤之一,也是癌症患者死亡的第二大主要原因。因此,准确诊断和有效治疗恶性肿瘤对 HCC 患者非常关键。具有超灵敏成像信号和高光热转换效率的声纳米颗粒是实现这一目标的一种新的、有前途的方法。在本研究中,我们通过将染料封装在由 DSPE-PEG 修饰的脂质体中来合成基于 IR-1061 染料的新型脂质纳米颗粒。我们进行了一系列实验,以研究新型纳米颗粒(Polipo-IR NP)在荷 HCC 裸鼠中的 PA 诊断性能、手术导航和光热治疗(PTT)能力。结果表明,我们的新型纳米颗粒在 1064nm 波长处表现出很强的激光能量吸收,高光热转换效率(45.25%)和超灵敏的 PA 信号。体内 PA 研究表明,所提出的纳米颗粒可以在 3h 注射后以 5.98±0.23 的强信噪比进行非侵入性和准确的肿瘤诊断,并能成功地在术中进行肿瘤的根治性切除。此外,PTT 测试证明了由于其高光热转换效率,具有显著的癌细胞杀伤能力。体外和体内实验也验证了其优异的光稳定性和高生物相容性。因此,基于 IR-1061 染料的我们提出的 NIR-II PA 和 PTT 纳米颗粒有可能为理解纳米医学中的多甲川染料提供新的见解,并将极大地有益于 HCC 患者的早期诊断和治疗。

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