利用负载阿霉素的金属有机框架涂层磁性纳米颗粒精准治疗结肠癌

2024年9月，浙江大学材料科学与工程学院；伊利诺伊大学芝加哥分校药学院药学系；浙江大学动物科学学院应用生物资源研究所，浙江蚕蜂资源利用与创新重点实验室 (School of Materials Science &Engineering,Zhejiang University, Hangzhou, Zhejiang 310027, China；Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, 60607, United States；Key Laboratory of Silkworm and Bee Resource Utilization and Innovation of Zhejiang Province,Institute of Applied Bioresource Research, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058,China;) Honglin Jiang老师研究团队在《Acs Applied Materials & Interfaces》上发表论文：

“Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles”

“利用负载阿霉素的金属有机框架涂层磁性纳米颗粒精准治疗结肠癌”

Abstract：

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe₃O₄ magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe₃O₄@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe₃O₄@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe₃O₄@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe₃O₄@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe₃O₄@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

摘要：

由于传统化疗药物缺乏特异性和选择性，其疗效有限，副作用明显，因此新的策略对于改善癌症治疗效果至关重要。在这里，我们成功地设计了包裹有沸石咪唑酸框架-8 （ZIF-8）的Fe3O4磁性纳米颗粒。由于ZIF-8的多孔性，所得到的纳米复合材料（Fe3O4@ZIF-8）能够有效吸附大量的阿霉素（DOX）。负载药物的纳米颗粒Fe3O4@ZIF-8/DOX在外部磁场引导下，在SW620结肠癌小鼠的肿瘤部位表现出显著的积累。在肿瘤的酸性微环境中，ZIF-8框架崩溃，释放DOX并有效诱导肿瘤细胞死亡，从而抑制癌症进展，同时不会引起不良副作用，这一点得到了各种体外和体内表征的证实。与游离DOX相比，Fe3O4@ZIF-8/DOX纳米颗粒在结肠癌治疗中表现出疗效。我们的研究结果表明，Fe3O4@ZIF-8有望成为小分子药物吸附的载体，其铁磁特性提供了药物靶向能力，从而在相同药物剂量下增强对肿瘤的治疗效果。Fe3O4@ZIF-8具有良好的生物相容性，具有作为靶向癌症化疗药物载体的潜力。我们的工作表明，磁性靶向和酸反应性的结合对于推进精确纳米医学中的靶向癌症治疗具有很大的希望。

该论文中，SW620的体外培养是使用Ausbian特级胎牛血清完成的。