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基于普鲁士蓝纳米颗粒的多功能诊疗试剂用于肿瘤靶向和 MRI 引导的光动力/光热联合治疗。

Multifunctional theranostic agents based on prussian blue nanoparticles for tumor targeted and MRI-guided photodynamic/photothermal combined treatment.

机构信息

Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, People's Republic of China.

出版信息

Nanotechnology. 2020 Mar 27;31(13):135101. doi: 10.1088/1361-6528/ab5d84. Epub 2019 Nov 29.

DOI:10.1088/1361-6528/ab5d84
PMID:31783383
Abstract

The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM s), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T-MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.

摘要

光动力或光热模式的独立性给肿瘤治疗的成功带来了困难。在本研究中,开发了一种多功能纳米治疗剂 PDE-Ce6-HA,用于肿瘤靶向和 MRI 引导的光动力/光热联合治疗(PDT/PTT)。为此,普鲁士蓝的近红外吸收纳米粒子被聚多巴胺包覆,并成功地与氯乙酮(Ce6)共轭以产生活性氧(ROS)。所得的纳米粒子,记为 PDE-Ce6,然后通过静电相互作用用透明质酸(HA)修饰,得到最终的治疗剂 PDE-Ce6-HA NPs。PDE-Ce6-HA NPs 不仅表现出高胶体稳定性、良好的生物相容性和合适的横向弛豫率(0.54 mM s),而且在近红外光照射下具有高的光热转换效率(40.4%)和优异的 ROS 生成效率。共聚焦显微镜图像显示,PDE-Ce6-HA 通过透明质酸介导的内吞作用被 CD44 过表达的 HeLa 细胞选择性摄取。同时,体外抗癌评价证实了 PDE-Ce6-HA 对癌细胞的显著光动力和光热联合效应。此外,PDE-Ce6-HA 导致肿瘤部位 T-MRI 对比增加。此外,体内抗肿瘤评价证明,PDE-Ce6-HA 在 808 和 670nm 激光下均表现出明显高于单独 PTT 或 PDT 的肿瘤生长抑制作用。因此,PDE-Ce6-HA 适用于肿瘤靶向和 MRI 引导的光动力/光热联合治疗。

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