Munawwar Aasma, Sajjad Amna, Rasul Azhar, Sattar Mehran, Jabeen Farhat
Department of Zoology, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Pharmaceuticals (Basel). 2023 Jul 10;16(7):986. doi: 10.3390/ph16070986.
Cancer therapies based on nanoparticles with a loaded drug can overcome the problem of the drug's toxic effects in the traditional chemotherapeutic approach. In this study, we loaded LLY-507, a potent inhibitor of SMYD2, a methyltransferase enzyme, on iron oxide nanoparticles (IONPs). The prepared nanoparticles were characterized by microscopic analysis, loading efficiency, and drug release studies. Microscopic examination revealed an average grain size of 44 nm. The in vitro effect of LLY-507-IONPs, LLY-507, and IONPs was determined by MTT analysis (A549 cells) and hemolysis studies. IONPs have almost negative hemolytic activity in blood. The cell viability assay revealed IC50 values of both LLY-507 alone and LLY-507-loaded IONPs against A549; the lower value of the drug loaded on NPs (0.71 µg/mL alone and 0.53 µg/mL loaded on NPs) shows strong synergistic anticancer potential. We further tested the role of loaded NPs in a urethane-induced lung cancer mouse model (n = 40 mice in three independent trials, 20 mice in control group) to check the role of SMYD2 at various time points of lung cancer development. The loss of SMYD2 due to LLY-507 suppressed tumor growth, emphysema, hemorrhage, and congestion considerably. Hence, it can be concluded that the SMYD2 inhibitor has an anti-inflammatory effect on the mouse lung and suppresses tumor growth by inhibiting the SMYD2 protein.
基于负载药物的纳米颗粒的癌症治疗方法可以克服传统化疗方法中药物毒性作用的问题。在本研究中，我们将SMYD2（一种甲基转移酶）的强效抑制剂LLY-507负载到氧化铁纳米颗粒（IONPs）上。通过显微镜分析、负载效率和药物释放研究对制备的纳米颗粒进行了表征。显微镜检查显示平均粒径为44纳米。通过MTT分析（A549细胞）和溶血研究确定了LLY-507-IONPs、LLY-507和IONPs的体外作用。IONPs在血液中几乎具有负溶血活性。细胞活力测定显示单独的LLY-507和负载LLY-507的IONPs对A549的IC50值；负载在纳米颗粒上的药物的较低值（单独为0.71微克/毫升，负载在纳米颗粒上为0.53微克/毫升）显示出强大的协同抗癌潜力。我们进一步在尿烷诱导的肺癌小鼠模型中测试了负载纳米颗粒的作用（在三项独立试验中有40只小鼠，对照组中有20只小鼠），以检查SMYD2在肺癌发展的各个时间点的作用。由于LLY-507导致的SMYD2缺失显著抑制了肿瘤生长、肺气肿、出血和充血。因此，可以得出结论，SMYD2抑制剂对小鼠肺部具有抗炎作用，并通过抑制SMYD2蛋白来抑制肿瘤生长。
