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基于载吲哚菁绿的脂质-聚合物纳米粒的尺寸来提高药物在肿瘤中的积累和光热疗效。

Improving drug accumulation and photothermal efficacy in tumor depending on size of ICG loaded lipid-polymer nanoparticles.

机构信息

Guangdong Key Laboratory of Nanomedicine & Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Chinese Academy of Sciences, Shenzhen 518055, PR China.

Guangdong Key Laboratory of Nanomedicine & Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Department of Chemistry, Guangdong Medical College, Dongguan 523808, PR China.

出版信息

Biomaterials. 2014 Jul;35(23):6037-46. doi: 10.1016/j.biomaterials.2014.04.019. Epub 2014 Apr 26.

DOI:10.1016/j.biomaterials.2014.04.019
PMID:24776486
Abstract

A key challenge to strengthen anti-tumor efficacy is to improve drug accumulation in tumors through size control. To explore the biodistribution and tumor accumulation of nanoparticles, we developed indocyanine green (ICG) loaded poly (lactic-co-glycolic acid) (PLGA) -lecithin-polyethylene glycol (PEG) core-shell nanoparticles (INPs) with 39 nm, 68 nm and 116 nm via single-step nanoprecipitation. These INPs exhibited good monodispersity, excellent fluorescence and size stability, and enhanced temperature response after laser irradiation. Through cell uptake and photothermal efficiency in vitro, we demonstrated that 39 nm INPs were more easily be absorbed by pancreatic carcinoma tumor cells (BxPC-3) and showed better photothermal damage than that of 68 nm and 116 nm size of INPs. Simultaneously, the fluorescence of INPs offered a real-time imaging monitor for subcellular locating and in vivo metabolic distribution. Near-infrared imaging in vivo and photothermal therapy illustrated that 68 nm INPs showed the strongest efficiency to suppress tumor growth due to abundant accumulation in BxPC-3 xenograft tumor model. The findings revealed that a nontoxic, size-dependent, theranostic INPs model was built for in vivo cancer imaging and photothermal therapy without adverse effect.

摘要

提高药物在肿瘤中的积累是增强抗肿瘤疗效的一个关键挑战。为了探索纳米粒子的生物分布和肿瘤积累,我们通过一步法纳米沉淀法制备了载有吲哚菁绿(ICG)的聚(乳酸-共-乙醇酸)(PLGA)-卵磷脂-聚乙二醇(PEG)核壳纳米粒子(INPs),其粒径分别为 39nm、68nm 和 116nm。这些 INPs 表现出良好的单分散性、优异的荧光性能和尺寸稳定性,并且在激光照射后表现出增强的温度响应。通过体外细胞摄取和光热效率实验,我们证明 39nm 的 INPs 更容易被胰腺癌肿瘤细胞(BxPC-3)吸收,并且比 68nm 和 116nm 尺寸的 INPs 具有更好的光热损伤效果。同时,INPs 的荧光提供了用于亚细胞定位和体内代谢分布的实时成像监测。体内近红外成像和光热治疗表明,由于在 BxPC-3 异种移植肿瘤模型中大量积累,68nm 的 INPs 表现出最强的抑制肿瘤生长的效率。这些发现表明,构建了一种无毒、尺寸依赖性的治疗性 INPs 模型,用于体内癌症成像和光热治疗,而无不良反应。

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