Disulfiram-loaded copper sulfide nanoparticles for potential anti-glioma therapy
Disulfiram-loaded copper sulfide nanoparticles for potential anti-glioma therapy
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负载双硫仑的硫化铜纳米粒子用于潜在的抗神经胶质瘤治疗
DOI：
10.1016/j.ijpharm.2021.120978
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发表时间：
2021-08-14
影响因子：
5.8
通讯作者：
Yao, Qing
中科院分区：
文献类型：
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作者：
Lan, Qing-Hua;Du, Chu-Chu;Yao, Qing
双硫仑（DSF）是一种有效的铜（Cu 2+）依赖性抗肿瘤药物。在本研究中，我们探索了转铁蛋白（Tf）修饰的DSF/硫化铜（CuS）纳米复合物（Tf-DSF/CuS）用于胶质瘤治疗的用途。Tf用作胶质瘤靶向基序，DSF用作抗癌剂，CuS用作Cu 2+离子源和光热剂。通过金属螯合作用将DSF负载在CuS上，并在酸性条件下从纳米复合物中释放出来。Tf-DSF/CuS复合物在体外表现出较强的细胞毒作用。值得注意的是，细胞毒活性与pH触发的Cu 2+释放相关，这引发了DSF的非毒性到毒性的转换。超声靶向微泡破坏（UTMD）技术用于静脉注射Tf-DSF/CuS在胶质瘤原位肿瘤中的高选择性积聚，与游离药物和非靶向DSF/CuS组相比。磁共振成像和病理学检查表明，Tf-DSF/CuS有效地抑制肿瘤生长，抑制率接近85%。此外，DSF负载不损害CuS纳米颗粒的光热转换能力。在808 nm激光照射下，评价Tf-DSF/CuS的光热消融治疗效果。这些发现表明基于硫化铜的双硫仑纳米颗粒是用于抗胶质瘤治疗的有效药剂。
Disulfiram (DSF) is an effective copper (Cu2+)-dependent antitumor agent. In the present study, we explored use of transferrin (Tf)-modified DSF/copper sulfide (CuS) nanocomplex (Tf-DSF/CuS) for glioma therapy. Tf was used as glioma targeting motifs, DSF as an anticancer agent, and CuS as a source of Cu2+ ions and a photothermal agent. DSF was loaded on CuS by metal-chelation, and released from the nanocomplex under acidic condition. The Tf-DSF/CuS complex exhibited high cytotoxic effect in vitro. Notably, cytotoxic activity was correlated with pH triggered release of Cu2+ which initiated non-toxicity to toxicity switch of DSF. Ultrasound-targeted microbubble destruction (UTMD) technique was used for highly selective accumulation of intravenous injec-ted Tf-DSF/CuS in the glioma orthotopic tumor as compared with the free drugs and non-targeted DSF/CuS groups. Magnetic resonance imaging and pathological examinations showed that Tf-DSF/CuS effectively sup-pressed tumor growth, with an inhibition ratio of similar to 85%. Additionally, DSF load did not compromise photo-thermal conversion ability of CuS nanoparticles. Efficacy of the photothermal ablation therapy of Tf-DSF/CuS was evaluated under 808 nm laser irradiation both in vitro and in vivo. These findings show that copper-sulfide based disulfiram nanoparticles are effective agents for anti-glioma therapy.