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载锰聚多巴胺纳米粒子作为磁共振成像和光热/化学动力学联合铁死亡治疗胃癌的诊疗一体化试剂。

Manganese-containing polydopamine nanoparticles as theranostic agents for magnetic resonance imaging and photothermal/chemodynamic combined ferroptosis therapy treating gastric cancer.

机构信息

Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Drug Deliv. 2022 Dec;29(1):1201-1211. doi: 10.1080/10717544.2022.2059124.

Abstract

Gastric cancer (GC) is a serious disease with high morbidity and mortality rates worldwide. Chemotherapy plays a key role in GC treatment, while inevitable drug resistance and systematic side effects hinder its clinical application. Fenton chemistry-based chemodynamic therapy (CDT) has been used as a strategy for cancer ferroptosis, and the CDT efficiency could be enhanced by photothermal therapy (PTT). With the trend of treatment and diagnosis integration, the combination of magnetic resonance imaging (MRI) and CDT/PTT exhibits enormous progress. Herein, we constructed a platform based on PEGylated manganese-containing polydopamine (PDA) nanoparticles, named as PEG-PDA@Mn (PP@Mn) NPs. The PP@Mn NPs were stable and globular. Furthermore, they demonstrated near-infrared (NIR)-triggered PTT and Fenton-like reaction-based CDT effects and T1-weighted MRI capabilities. According to studies, the PP@Mn NPs trigger ferroptosis in cancer cells by producing abundant reactive oxygen species (ROS) via a Fenton-like reaction combined with PTT. Furthermore, studies showed that, under MRI guidance, the PP@Mn NPs combined with the PTT at the tumor region, have CDT anti-tumor effect. In conclusion, the PP@Mn NPs could provide an effective strategy for CDT/PTT synergistic ferroptosis therapy for GC.

摘要

胃癌(GC)是一种发病率和死亡率都很高的严重疾病。化疗在 GC 治疗中起着关键作用,但其不可避免的耐药性和系统副作用阻碍了其临床应用。基于 Fenton 化学的化学动力学疗法(CDT)已被用作癌症铁死亡的策略,光热疗法(PTT)可以增强 CDT 的效率。随着治疗和诊断一体化的趋势,磁共振成像(MRI)与 CDT/PTT 的结合取得了巨大进展。在此,我们构建了一个基于聚乙二醇化含锰聚多巴胺(PDA)纳米粒子的平台,命名为 PEG-PDA@Mn(PP@Mn)NPs。PP@Mn NPs 稳定且呈球形。此外,它们表现出近红外(NIR)触发的 PTT 和基于 Fenton 样反应的 CDT 效应以及 T1 加权 MRI 能力。研究表明,PP@Mn NPs 通过 Fenton 样反应与 PTT 结合产生丰富的活性氧(ROS),从而引发癌细胞的铁死亡。此外,研究表明,在 MRI 引导下,PP@Mn NPs 与肿瘤区域的 PTT 联合使用,具有 CDT 抗肿瘤作用。总之,PP@Mn NPs 为 GC 的 CDT/PTT 协同铁死亡治疗提供了一种有效的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/916a/9004524/50b709779b64/IDRD_A_2059124_SCH0001_C.jpg

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