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Cisplatin-loaded hollow gold nanoparticles for laser-triggered release.
Cancer Nanotechnology ( IF 5.7 ) Pub Date : 2018-08-03 , DOI: 10.1186/s12645-018-0041-9
Chiyi Xiong 1 , Wei Lu 1, 2 , Min Zhou 1, 3 , Xiaoxia Wen 1 , Chun Li 1
Affiliation  

Hollow gold nanoparticles (HGNPs) exposed to near-infrared (NIR) light yield photothermal effects that can trigger a variety of biological effects for potential biomedical applications. However, the mechanism of laser-triggered drug release has not been studied before. A tripeptide Ac-Glu-Glu-Cys-NH2 (Ac-EEC) was directly linked to the surface of HGNPs. The EEC-HGNPs conjugate was then complexed with cisplatin Pt(II) to give Ac-EEC(Pt)-HGNPs. Folic acid was introduced to the gold surface of Ac-EEC-HGNPs through a thioctic acid-terminated polyethylene glycol linker (F-PEG-TA) followed by complexation with Pt(II) to give F-Ac-EEC(Pt)-HGNPs. Laser treatment was instituted with a 15-ns pulsed laser at a repetition rate of 10 Hz. The released Pt(II) was quantified by inductively coupled plasma mass spectroscopy, and the nature of the released Pt-containing species was characterized by liquid chromatography–mass spectroscopy. The cytotoxicity was studied using the MTT assay. Pt(II) was released from Ac-EEC(Pt)-HGNPs via two modes: (1) sustained release through an inverse ligand exchange reaction with chloride ions and (2) rapid release through cleavage of the Au–S bond between the tripeptide linker and Au surface upon NIR laser irradiation. The folate (F) conjugate of the nanoconstruct, F-Ac-EEC(Pt)-HGNPs, in combination with laser treatment showed a significantly greater effect on cell mortality against folate-overexpressing human epidermoid carcinoma KB cells than F-Ac-ECC(Pt)-HGNPs alone after 24 h of incubation. These results demonstrate that the photothermal property of HGNPs can be used for dual-modality photothermal therapy and NIR laser-triggered platinum-based chemotherapy.

中文翻译:

载有顺铂的中空金纳米粒子,用于激光触发释放。

暴露在近红外 (NIR) 光下的空心金纳米粒子 (HGNP) 会产生光热效应,从而触发潜在生物医学应用的各种生物效应。然而,之前尚未研究过激光触发药物释放的机制。三肽 Ac-Glu-Glu-Cys-NH2 (Ac-EEC) 直接连接到 HGNPs 的表面。然后将 EEC-HGNPs 缀合物与顺铂 Pt(II) 复合,得到 Ac-EEC(Pt)-HGNPs。叶酸通过硫辛酸封端的聚乙二醇接头 (F-PEG-TA) 引入 Ac-EEC-HGNPs 的金表面,然后与 Pt(II) 络合得到 F-Ac-EEC(Pt)-HGNPs . 激光治疗采用 15 ns 脉冲激光,重复频率为 10 Hz。通过电感耦合等离子体质谱对释放的 Pt(II) 进行量化,释放的含铂物质的性质通过液相色谱-质谱法进行表征。使用MTT法研究细胞毒性。Pt(II) 通过两种模式从 Ac-EEC(Pt)-HGNPs 中释放:(1) 通过与氯离子的逆配体交换反应持续释放;(2) 通过三肽之间的 Au-S 键断裂快速释放NIR 激光照射后的接头和金表面。纳米结构 F-Ac-EEC(Pt)-HGNPs 的叶酸 (F) 缀合物与激光治疗相结合,对过表达叶酸的人表皮样癌 KB 细胞的细胞死亡率的影响显着高于 F-Ac-ECC (孵育 24 小时后单独使用 Pt)-HGNP。
更新日期:2018-08-03
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