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Development of a nano-drug delivery system based on mesoporous silica and its anti-lymphoma activity
Applied Nanoscience Pub Date : 2020-06-04 , DOI: 10.1007/s13204-020-01465-0
Qiangqiang Zhao , Bin Wu , Yinghui Shang , Xueyuan Huang , Hang Dong , Haiting Liu , Wansong Chen , Rong Gui , Jian Li

Although current treatment strategies including systemic chemotherapy, local radiotherapy, biological immunology, and surgical resection have improved the remission rate of non-Hodgkin’s lymphoma (NHL) patients, the recurrence rate of the disease remains high, and the remission rate of retreatment after recurrence is low. Exploring and discovering new strategies for treating NHL has become a critical problem to be solved. Harmine (HM) has demonstrated anti-tumor activity; however, like most traditional Chinese medicines, it does not exhibit targeting behavior and is characterized by poor pharmacokinetics, which limits its clinical application. To solve these problems, we constructed a new anti-lymphoma drug delivery system using mesoporous silica nanoparticles (MSNs) loaded with HM. This complex passively targets the tumor tissue, shows pH-responsive drug release, is non-toxic, and has efficient anti-lymphoma properties. Compared with free HM, the tumor inhibition rates of the HM@MSNs was 72.36 ± 5.16% and inhibition of the formation of lymphoma cell clones. Likewise, HM@MSNs could up-regulate the apoptosis rate of Daudi cells to 23.61 ± 0.88%. Moreover, it can inhibit the activation of NF-κB and production of inflammatory cytokines TNF-α (20.9 ± 1.8%) and IL-6 (22.7 ± 2.1%). In nude mice transplanted tumor model treated with HM@MSNs, TUNEL exhibited diffuse red fluorescence in vivo, suggesting that HM@MSNs could significantly induce tumor tissue apoptosis, and HM@MSNs-treated tumor tissue significantly decreased the fluorescence signals of NF-κB p65, TNF-α and IL-6, indicating that it down-regulated the expression of the mentioned three factors, and HM@MSNs significantly inhibited the proliferation of tumor volume. The mentioned results suggested that HM@MSNs finally induced apoptosis of lymphoma cells via anti-inflammatory mechanism. In general, MSNs loaded with HM can be potentially applied to the treatment of NHL.



中文翻译:

基于中孔二氧化硅的纳米药物递送系统的开发及其抗淋巴瘤活性

尽管目前的治疗策略包括全身化疗,局部放疗,生物免疫学和外科手术切除术已提高了非霍奇金淋巴瘤(NHL)患者的缓解率,但该疾病的复发率仍然很高,复发后再治疗的缓解率仍然很高。低。探索和发现治疗NHL的新策略已成为亟待解决的关键问题。Harmine(HM)具有抗肿瘤活性。但是,与大多数传统中药一样,它没有表现出靶向作用,并且具有药代动力学差的特点,这限制了其临床应用。为了解决这些问题,我们使用负载了HM的中孔二氧化硅纳米颗粒(MSN)构建了一种新的抗淋巴瘤药物递送系统。这种复合物被动地靶向肿瘤组织,显示出对pH敏感的药物释放,无毒且具有有效的抗淋巴瘤特性。与游离HM相比,HM @ MSNs的抑瘤率为72.36±5.16%,对淋巴瘤细胞克隆的形成有抑制作用。同样,HM @ MSNs可以将Daudi细胞的凋亡率上调至23.61±0.88%。此外,它可以抑制NF-κB的活化和炎性细胞因子TNF-α(20.9±1.8%)和IL-6(22.7±2.1%)的产生。在用HM @ MSNs处理的裸鼠移植的肿瘤模型中,TUNEL体内显示出弥漫性红色荧光,这表明HM @ MSNs可以显着诱导肿瘤组织凋亡,而HM @ MSNs处理的肿瘤组织则显着降低NF-κBp65的荧光信号。 ,TNF-α和IL-6,表明它下调了上述三个因子的表达,HM @ MSNs显着抑制肿瘤体积的增殖。上述结果提示HM @ MSNs通过抗炎机制最终诱导淋巴瘤细胞凋亡。通常,载有HM的MSN可以潜在地应用于NHL的治疗。

更新日期:2020-06-04
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