He Zi, Su Huiling, Shen Yuqing, Shi Wei, Liu Xin, Liu Yang, Zhang Fuhui, Zhang Yansheng, Sun Yanan, Ge Dongtao
Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University Xiamen 361005 China
Xiamen Maternal and Child Health Hospital Xiamen 361003 China.
RSC Adv. 2019 Mar 29;9(18):9968-9982. doi: 10.1039/c9ra01289c. eCollection 2019 Mar 28.
The photothermal-chemical combination therapy is a promising approach for cancer treatment, however, chemotherapy often causes severe toxic and side effects on normal tissues. Herein, tumor-specific FeOOH@PNE-Art nanoparticles were fabricated coating poly(norepinephrine) (PNE) on FeOOH nanoparticles, followed by loading of artemisinin (Art). The as-prepared nanoparticles exhibited excellent biocompatibility, strong near-infrared (NIR) absorbance and pH-responsive synchronous release of Art and iron ions. The released iron ions could not only supply iron ions in cancer cells which mediate endoperoxide bridge cleavage of Art and generate reactive oxygen species (ROS), but also react with HO at tumour sites the Fenton reaction and produce hydroxyl radicals, inducing a tumour-specific killing. Moreover, owing to the synchronous release of Art and iron ions as well as the low leakage of iron ions, FeOOH@PNE-Art nanoparticles showed extremely low toxicity to normal tissue. Under NIR light irradiation, the tumours in FeOOH@PNE-Art injected mice were thoroughly eliminated after 7 days of treatment and no tumour recurrence was found 30 days after treatment, manifesting very high efficacy of combination therapy.
光热化学联合疗法是一种很有前景的癌症治疗方法，然而，化疗常常会对正常组织造成严重的毒副作用。在此，制备了肿瘤特异性的FeOOH@PNE-Art纳米颗粒，即在FeOOH纳米颗粒上包覆聚去甲肾上腺素（PNE），随后负载青蒿素（Art）。所制备的纳米颗粒表现出优异的生物相容性、强烈的近红外（NIR）吸收以及pH响应性的青蒿素和铁离子同步释放。释放出的铁离子不仅能为癌细胞提供铁离子，介导青蒿素内过氧化物桥的裂解并产生活性氧（ROS），还能在肿瘤部位与HO通过芬顿反应生成羟基自由基，从而实现肿瘤特异性杀伤。此外，由于青蒿素和铁离子的同步释放以及铁离子的低泄漏率，FeOOH@PNE-Art纳米颗粒对正常组织表现出极低的毒性。在近红外光照射下，注射了FeOOH@PNE-Art的小鼠肿瘤在治疗7天后被彻底消除，且在治疗30天后未发现肿瘤复发，显示出联合疗法的高效性。
