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ICG/5-Fu 共包封温度刺激响应纳米凝胶药物递送平台用于化学光热/光动力协同治疗。

ICG/5-Fu coencapsulated temperature stimulus response nanogel drug delivery platform for chemo-photothermal/photodynamic synergetic therapy.

机构信息

Department of Polymer Materials, 12646Zhejiang Sci-Tech University, Hangzhou, China.

出版信息

J Biomater Appl. 2021 Oct;36(4):565-578. doi: 10.1177/0885328220988419. Epub 2021 Jan 24.

Abstract

The multiple diagnosis and treatment mechanisms of chemotherapy combined with photothermal/photodynamic therapy have very large application prospects in the field of cancer treatment. Therefore, in order to achieve effective and safe antitumour treatment, it is necessary to design an intelligent responsive polymer nanoplatform as a drug delivery system. Herein, the thermosensitive poly-N-isopropylacrylamide (PNIPAM) nanogel particles were prepared by soap-free emulsion polymerization and loaded with a large amount of photosensitizer indocyanine green (ICG) and anticarcinogen 5-fluorouracil (5-Fu), which effectively to realize the cooperative chemotherapy and photothermal/photodynamic therapy for tumours. The 5-Fu@ICG-PNIPAM nanogels significantly improved the bioavailability of the drug and achieved controlled release. In addition, under near-infrared laser (NIR) irradiation at 808 nm, 5-Fu@ICG-PNIPAM nanogels generated lots of heat and reactive oxygen, which significantly enhanced cellular uptake and antitumour treatment effects. The results showed that 5-Fu@ICG-PNIPAM nanogels were effectively endocytosed by HeLa cells, which also enhanced the drug's entrance into the nucleus. Moreover, compared with alone chemotherapy or photothermal/photodynamic therapy, 5-Fu@ICG-PNIPAM nanogels significantly increased cytotoxicity under NIR irradiation, suggesting that chemotherapy and photothermal/photodynamic synergistic therapy had excellent antitumour properties. Therefore, this temperature-responsive nanogel platform probably has great application prospects in clinical antitumour treatment.

摘要

化疗联合光热/光动力疗法的多重诊断和治疗机制在癌症治疗领域具有非常大的应用前景。因此,为了实现有效的、安全的抗肿瘤治疗,有必要设计一种智能响应性聚合物纳米平台作为药物传递系统。在此,通过无皂乳液聚合法制备了温敏性聚 N-异丙基丙烯酰胺(PNIPAM)纳米凝胶颗粒,并负载了大量的光敏剂吲哚菁绿(ICG)和抗癌药 5-氟尿嘧啶(5-Fu),可有效实现肿瘤的协同化疗和光热/光动力治疗。5-Fu@ICG-PNIPAM 纳米凝胶显著提高了药物的生物利用度并实现了控制释放。此外,在 808nm 的近红外激光(NIR)照射下,5-Fu@ICG-PNIPAM 纳米凝胶产生了大量的热和活性氧,显著增强了细胞摄取和抗肿瘤治疗效果。结果表明,5-Fu@ICG-PNIPAM 纳米凝胶可被 HeLa 细胞有效内吞,这也增强了药物进入细胞核的能力。而且,与单独的化疗或光热/光动力治疗相比,在 NIR 照射下,5-Fu@ICG-PNIPAM 纳米凝胶显著增加了细胞毒性,表明化疗和光热/光动力协同治疗具有优异的抗肿瘤特性。因此,这种温度响应性纳米凝胶平台在临床抗肿瘤治疗中可能具有广阔的应用前景。

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