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用于磁共振成像引导的协同化学-光热疗法的双刺激响应性、聚合物微球包裹的硫化铜纳米颗粒

Dual-Stimuli-Responsive, Polymer-Microsphere-Encapsulated CuS Nanoparticles for Magnetic Resonance Imaging Guided Synergistic Chemo-Photothermal Therapy.

作者信息

Zhang Li, Yang Zhe, Zhu Wei, Ye Zhilan, Yu Yiming, Xu Zushun, Ren Jinghua, Li Penghui

机构信息

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei University, Wuhan, Hubei 430062, China.

Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China.

出版信息

ACS Biomater Sci Eng. 2017 Aug 14;3(8):1690-1701. doi: 10.1021/acsbiomaterials.7b00204. Epub 2017 Jul 6.

DOI:10.1021/acsbiomaterials.7b00204
PMID:33429651
Abstract

Integrating biomedical imaging and multimodal therapies into one platform for enhanced anticancer efficacy is of great significance. Herein, a core/shell structured nanotheranostic (CuS@copolymer) for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy was simply prepared via emulsifier-free emulsion polymerization with the full participation of hydrophilic CuS NPs, styrene (St), -isopropylacrylamide (NIPAm), methacrylic acid (MAA), and polymerizable rare earth complex (Gd(AA)phen). The synthesized multifunctional microspheres with excellent biocompatibility exhibited high loading capacity (15.3 wt %) for DOX·HCl and excellent drug release under low pH and high temperature. The photosensitive CuS cores which can simultaneously efficiently absorb near-infrared (NIR) light and convert NIR light to fatal heat, leading to a synergistic therapeutic effect combined photothermal therapy (PTT) with chemotherapy. Moreover, the temperature sensitive copolymer attached onto the CuS nanoparticles was able to be productively infected by the thermal effect and give rise to a highly controllable DOX release. Furthermore, the CuS@copolymer/DOX showed an enhanced therapeutic efficacy against 4T1 cells than separate photothermal therapy or chemotherapy. Additionally, the drug delivery procedure could be visualized by in vivo MR images and the longitudinal relaxivity () was calculated to be 10.72 mM s. These results suggest the CuS@copolymer microspheres highly attractive candidates for biomedical applications.

摘要

将生物医学成像和多模态疗法整合到一个平台以提高抗癌疗效具有重要意义。在此,通过无乳化剂乳液聚合,在亲水性硫化铜纳米颗粒、苯乙烯(St)、N-异丙基丙烯酰胺(NIPAm)、甲基丙烯酸(MAA)和可聚合稀土配合物(钆(AA)菲咯啉)的充分参与下,简单制备了一种用于磁共振成像(MRI)引导的化疗-光热疗法的核/壳结构纳米诊疗剂(硫化铜@共聚物)。合成的具有优异生物相容性的多功能微球对盐酸多柔比星表现出高负载量(15.3 wt%),并在低pH和高温下具有优异的药物释放性能。光敏硫化铜核能够同时高效吸收近红外(NIR)光并将NIR光转化为致命热量,从而导致光热疗法(PTT)与化疗相结合的协同治疗效果。此外,附着在硫化铜纳米颗粒上的温度敏感共聚物能够被热效应有效影响,并导致高度可控的多柔比星释放。此外,硫化铜@共聚物/多柔比星对4T1细胞的治疗效果比单独的光热疗法或化疗增强。此外,药物递送过程可以通过体内磁共振图像可视化,纵向弛豫率()计算为10.72 mM s。这些结果表明硫化铜@共聚物微球是生物医学应用中极具吸引力的候选物。

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