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细胞穿透肽 TAT 增强近红外触发靶向纳米颗粒的细胞摄取用于联合化疗/光热/光动力治疗。

Enhanced cellular uptake of near-infrared triggered targeted nanoparticles by cell-penetrating peptide TAT for combined chemo/photothermal/photodynamic therapy.

机构信息

School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.

College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109738. doi: 10.1016/j.msec.2019.109738. Epub 2019 May 9.

DOI:10.1016/j.msec.2019.109738
PMID:31349475
Abstract

Recently, the emergence of cell-penetrating peptides (CPPs) like TAT has greatly improved the efficiency of cancer therapy by enhancing cellular uptake of nanomaterials. Here, we designed a near-infrared (NIR) triggered TAT-based targeted nanoplatform (cRGD@TAT-DINPs), which co-delivered anticancer drug doxorubicin (DOX) and biocompatible dye indocyanine green (ICG) to realize combined chemo/photothermal/photodynamic therapy of cancer in vitro. The resulting nanoparticles showed favorable monodispersity and colloidal stability. Impressively, the DOX could be released in a promoted manner once the nanoparticles were exposed to NIR light. Confocal laser scanning microscopy (CLSM) and flow cytometry analysis demonstrated an immensely enhanced cellular accumulation of DOX after the simultaneous introduction of targeted ligand cRGD and CPP TAT. In addition, the obtained nanoparticles exhibited explosive temperature elevation and reactive oxygen species (ROS) generation mediated by encapsulated ICG under NIR irradiation, and in vitro cytotoxicity assay confirmed the cRGD@TAT-DINPs had an increasing cytotoxicity and excellent synergistic inhibition capacity. Thus, TAT-based nanosystems provide a high-efficient drug delivery strategy for optimizing combined therapy efficiency of cancer.

摘要

最近,像 TAT 这样的细胞穿透肽 (CPP) 的出现通过增强纳米材料的细胞摄取,极大地提高了癌症治疗的效率。在这里,我们设计了一种近红外 (NIR) 触发的基于 TAT 的靶向纳米平台 (cRGD@TAT-DINPs),它共递送抗癌药物阿霉素 (DOX) 和生物相容性染料吲哚菁绿 (ICG),以实现体外联合化学/光热/光动力治疗癌症。所得纳米粒子表现出良好的单分散性和胶体稳定性。令人印象深刻的是,一旦纳米粒子暴露于近红外光,DOX 就可以以促进的方式释放。共聚焦激光扫描显微镜 (CLSM) 和流式细胞术分析表明,在同时引入靶向配体 cRGD 和 CPP TAT 后,DOX 的细胞摄取量大大增加。此外,所得纳米粒子在近红外照射下表现出由包封的 ICG 介导的爆炸式升温和活性氧 (ROS) 生成,体外细胞毒性试验证实 cRGD@TAT-DINPs 具有增强的细胞毒性和优异的协同抑制能力。因此,基于 TAT 的纳米系统为优化癌症联合治疗效率提供了一种高效的药物递送策略。

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