4.6 Article

Synthesis and Biological Evaluation of PEGylated MWO4 Nanoparticles as Sonodynamic AID Inhibitors in Treating Diffuse Large B-Cell Lymphoma

期刊

MOLECULES
卷 27, 期 21, 页码 -

出版社

MDPI
DOI: 10.3390/molecules27217143

关键词

activation-induced cytidine deaminase; inhibitors; PEGylated MWO4 nanoparticles; DLBCL treatment

资金

  1. Key Scientific Research Foundation of the Higher Education Institutions of Henan Province [22A320044, 22A320041]
  2. Key Scientific and Technological Project of Henan Province [212102310748]
  3. Startup Foundation for Doctor of Xinxiang Medical University [XYBSKYZZ202002, XYBSKYZZ202116]
  4. National Natural Science Foundation of China [22102049]

向作者/读者索取更多资源

Sonodynamic therapy using MWO4-PEG NPs shows promising inhibitory effects on activation-induced cytidine deaminase (AID) in diffuse large B-cell lymphoma. The interaction between reactive oxygen species and AID was investigated, and the NPs were found to effectively neutralize the extensive carcinogenesis caused by AID. Cell apoptosis and ROS generation in DLBCL cells treated with these NPs were observed to confirm their sonosensitivity and toxicity, indicating their potential as a treatment for AID-positive hematopoietic cancers.
Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its ability to overcome critical limitations, including low tissue-penetration depth and phototoxicity in photodynamic therapy (PDT). Biogenic metal oxide nanoparticles (NPs) have been used as anti-cancer drugs due to their biocompatibility properties with most biological systems. Here, sonosensitizer MWO4-PEG NPs (M = Fe Mn Co Ni) were synthesized as inhibitors to activation-induced cytidine deaminase (AID), thus neutralizing the extensive carcinogenesis of AID in diffuse large B-cell lymphoma (DLBCL). The physiological properties of these nanomaterials were examined using transmission electron microscopy (TEM). The inhibition of NPs to AID was primarily identified by the affinity interaction prediction between reactive oxygen species (ROS) and AID through molecular dynamics and molecular docking technology. The cell apoptosis and ROS generation in US-triggered NPs treated DLBCL cells (with high levels of AID) were also detected to indicate the sonosensitivity and toxicity of MWO4-PEG NPs to DLBCL cells. The anti-lymphoma studies using DLBCL and AID-deficient DLBCL cell lines indicated a concentration-dependent profile. The synthesized MWO4-PEG NPs in this study manifested good sonodynamic inhibitory effects to AID and well treatment for AID-positive hematopoietic cancers.

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