Dou Yuanyao, Zhang Yimin, Lin Caiyu, Han Rui, Wang Yubo, Wu Di, Zheng Jie, Lu Conghua, Tang Liling, He Yong
Department of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Front Bioeng Biotechnol. 2022 Sep 9;10:983677. doi: 10.3389/fbioe.2022.983677. eCollection 2022.
Multiple component integration to achieve both therapy and diagnosis in a single theranostic nanosystem has aroused great research interest in the medical investigator. This study aimed to construct a novel theranostic nanoplatform ferrite and ceria co-engineered mesoporous silica nanoparticles (Fe/Ce-MSN) antioxidant agent though a facile metal Fe/Ce-codoping approach in the MSN framework. The resulted Fe-incorporated ceria-based MSN nanoparticles possessing a higher Ce-to-Ce ratio than those revealed by ceria-only nanoparticles. The as-prepared Fe/Ce-MSN nanoparticles exhibited an excellent efficiency in scavenging reactive oxygen species (ROS), which is attributed to improving the superoxide dismutase (SOD) mimetics activity by increasing Ce content and maintaining a higher activity of catalase (CAT) mimetics including ferrite ion in nanoparticles. The fast Fe/Ce-MSN biodegradation, which is sensitive to the mild acidic microenvironment of inflammation, can accelerate Fe/Ce ion release, and the freed Fe ions enhanced T-weighted magnetic resonance imaging in the inflammation site. PEGylated Fe/Ce-MSN nanoparticles cell models significantly attenuated ROS-induced inflammation, oxidative stress, and apoptosis in macrophages by scavenging overproduced intracellular ROS. More importantly, Fe/Ce-MSN-PEG NPs exhibited significant anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) levels . Additionally, it can promote the macrophages polarization of pro-inflammatory M1 phenotype towards an anti-inflammatory M2 phenotype. Thus, the novel pH-responsive theranostic nanoplatform shows great promise for inflammation and oxidative stress-associated disease treatment.
在单个治疗诊断纳米系统中实现治疗与诊断的多组分整合,已引起医学研究人员的极大研究兴趣。本研究旨在通过在介孔二氧化硅纳米颗粒(MSN)框架中采用简便的金属铁/铈共掺杂方法,构建一种新型的治疗诊断纳米平台——铁氧体和二氧化铈共同工程化的介孔二氧化硅纳米颗粒(Fe/Ce-MSN)抗氧化剂。所得到的含铈铁基MSN纳米颗粒的铈/铈比高于仅含二氧化铈的纳米颗粒。所制备的Fe/Ce-MSN纳米颗粒在清除活性氧(ROS)方面表现出优异的效率,这归因于通过增加铈含量提高超氧化物歧化酶(SOD)模拟活性,并在纳米颗粒中维持包括铁氧体离子在内的过氧化氢酶(CAT)模拟物的较高活性。Fe/Ce-MSN的快速生物降解对炎症的轻度酸性微环境敏感,可加速铁/铈离子释放,释放的铁离子增强了炎症部位的T加权磁共振成像。聚乙二醇化的Fe/Ce-MSN纳米颗粒在细胞模型中通过清除细胞内过量产生的ROS,显著减轻了ROS诱导的巨噬细胞炎症、氧化应激和细胞凋亡。更重要的是,Fe/Ce-MSN-PEG纳米颗粒通过抑制脂多糖(LPS)诱导的肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平的表达,表现出显著的抗炎作用。此外,它可以促进巨噬细胞从促炎M1表型向抗炎M2表型极化。因此,这种新型的pH响应治疗诊断纳米平台在炎症和氧化应激相关疾病治疗方面显示出巨大的潜力。