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载硼替佐米的中空介孔硅纳米球对淋巴瘤发展的抗癌作用的改善。

The improved anticancer effects of Bortezomib-loaded hollow mesoporous silica nanospheres on lymphoma development.

机构信息

Department of Hematology, Centre Hospital of Cangzhou, Cangzhou, Hebei Province, China.

Department of Central Laboratory, Centre Hospital of Cangzhou, Cangzhou, Hebei Province, China.

出版信息

Aging (Albany NY). 2020 Dec 3;13(1):411-423. doi: 10.18632/aging.202146.

Abstract

As the first clinical proteasome inhibitor, Bortezomib (BTZ) has been reported to improve the outcome of lymphoma. However, due to the unstable property, low bioavailability, and hydrophobic properties of BTZ, it is needed to develop effective drug delivery systems to deliver BTZ into targeted cells or organs. Here we developed a bortezomib (BTZ)-loaded HMSNs (BTZ@HMSNs) system, which can sustain the release of BTZ in targeted tissues. assays showed that BTZ@HMSNs limited cell proliferation and augmented apoptosis of lymphoma SNK-1 cells. Moreover, BTZ@HMSNs significantly diminished migration and invasion of SNK-1 cells as compared with BTZ. In contrast to the upregulation of SHP-1, BTZ@HMSNs decreased the mRNA levels of , , and , which elicit oncogenic role in lymphoma development. Importantly, lymphoma mice model showed that BTZ@HMSNs significantly activated p53 signaling and reduced tumor volume and weight compared with free BTZ. Our data thus demonstrate that BTZ@HMSNs manifests improved tumor-suppressing effect and compared to free BTZ. We believe that HMSNs is a promising strategy for delivering therapeutic agents for cancer treatment.

摘要

硼替佐米(BTZ)作为首个临床蛋白酶体抑制剂,据报道可改善淋巴瘤的预后。然而,由于 BTZ 性质不稳定、生物利用度低和疏水性,需要开发有效的药物输送系统将 BTZ 递送到靶向细胞或器官。在这里,我们开发了一种硼替佐米(BTZ)负载的 HMSNs(BTZ@HMSNs)系统,可在靶向组织中持续释放 BTZ。 实验表明,BTZ@HMSNs 抑制淋巴瘤 SNK-1 细胞的增殖并促进其凋亡。此外,与 BTZ 相比,BTZ@HMSNs 显著减少了 SNK-1 细胞的迁移和侵袭。与 SHP-1 的上调相反,BTZ@HMSNs 降低了淋巴瘤发展中具有致癌作用的 、 和 的 mRNA 水平。重要的是,淋巴瘤小鼠模型表明,与游离 BTZ 相比,BTZ@HMSNs 显著激活了 p53 信号通路,减少了肿瘤体积和重量。因此,我们的数据表明,BTZ@HMSNs 与游离 BTZ 相比,表现出改善的肿瘤抑制作用 和 。我们相信 HMSNs 是用于癌症治疗的治疗剂递送的有前途的策略。

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