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肿瘤靶向碳点修饰的多刺激响应纳米系统用于化学-光协同治疗。

Multi-stimuli responsive nanosystem modified by tumor-targeted carbon dots for chemophototherapy synergistic therapy.

机构信息

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.

出版信息

J Colloid Interface Sci. 2019 Sep 15;552:639-650. doi: 10.1016/j.jcis.2019.05.085. Epub 2019 May 25.

Abstract

In this work, a tumor-targeted and multi-stimuli responsive drug delivery system combining infrared thermal imaging of cells with thermo-chemotherapy was developed. Oxidized mesoporous carbon nanoparticles (MCNs-COOH) with high photothermal conversion ability (photothermal transduction efficiency η = 27.4%) in near-infrared (NIR) region were utilized to encapsulate doxorubicin (DOX). The outer surfaces of MCNs-COOH were capped with multifunctional carbon dots (CD) as simultaneous smart gatekeepers, a tumor targeting moiety and a fluorescent probe. NIR laser irradiation killed cancer cells through NIR-light induced hyperthermia, facilitated chemotherapeutic drug release and enhanced the sensitivity of tumor cells to drugs. The therapeutic efficacy in two-dimensional (2D) and three-dimensional (3D) cells demonstrated that MC-CD loading DOX (MC-CD/DOX) had good chemo-photothermal synergistic antitumor effects (combination index of CI = 0.448). The biodistribution and pharmacodynamics experiments of MC-CD/DOX in the 4T1 tumor model indicated that MCNs-COOH prolonged the residence time of DOX in tumor tissues and therefore actualized effective synergistic photothermal chemotherapy. By combining these excellent capabilities, the tumor-targeted and multi-stimuli responsive drug delivery system can be utilized as a visible nanoplatform for chemophotothermal synergistic therapy.

摘要

在这项工作中,开发了一种结合细胞红外热成像与热化疗的肿瘤靶向多刺激响应药物传递系统。利用具有高光热转换能力(近红外区域的光热转导效率 η=27.4%)的氧化介孔碳纳米粒子(MCNs-COOH)来包裹阿霉素(DOX)。MCNs-COOH 的外表面被多功能碳点(CD)封端,作为同时的智能门控、肿瘤靶向部分和荧光探针。近红外激光照射通过近红外光诱导的热疗杀死癌细胞,促进化疗药物释放,并增强肿瘤细胞对药物的敏感性。在二维(2D)和三维(3D)细胞中的治疗效果表明,载有 DOX 的 MC-CD(MC-CD/DOX)具有良好的化疗-光热协同抗肿瘤作用(CI 值为 0.448)。MC-CD/DOX 在 4T1 肿瘤模型中的体内分布和药效学实验表明,MCNs-COOH 延长了 DOX 在肿瘤组织中的停留时间,从而实现了有效的协同光热化疗。通过结合这些优异的性能,肿瘤靶向多刺激响应药物传递系统可用作化学光热协同治疗的可视化纳米平台。

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