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近红外光/磁共振成像引导的无需氧气的无载体抗肿瘤纳米诊疗剂

NIR/MRI-Guided Oxygen-Independent Carrier-Free Anti-Tumor Nano-Theranostics.

作者信息

Gao Di, Shi Yupeng, Ni Jiahua, Chen Shuojia, Wang Ying, Zhao Bin, Song Manli, Guo Xiaoqing, Ren Xuechun, Zhang Xingcai, Tian Zhongmin, Yang Zhe

机构信息

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Henan Key laboratory of Functional Magnetic Resonance Imaging and Molecular Imaging Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, P. R. China.

出版信息

Small. 2022 Sep;18(36):e2106000. doi: 10.1002/smll.202106000. Epub 2021 Dec 2.

Abstract

Imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer treatment are beneficial for precise localization of the malignant lesions and combination of multiple cell killing mechanisms in eradicating stubborn thermal-resistant cancer cells. However, overcoming the adverse impact of tumor hypoxia on PDT efficacy remains a challenge. Here, carrier-free nano-theranostic agents are developed (AIBME@IR780-APM NPs) for magnetic resonance imaging (MRI)-guided synergistic PTT/thermodynamic therapy (TDT). Two IR780 derivatives are synthesized as the subject of nanomedicine to confer the advantages for the nanomedicine, which are by feat of amphiphilic IR780-PEG to enhance the sterical stability and reduce the risk from reticuloendothelial system uptake, and IR780-ATU to chelate Mn for T -weighted MRI. Dimethyl 2,2'-azobis(2-methylpropionate) (AIBME), acting as thermally decomposable radical initiators, are further introduced into nanosystems with the purpose of generating highly cytotoxic alkyl radicals upon PTT launched by IR780 under 808 nm laser irradiation. Therefore, the sequentially generated heat and alkyl radicals synergistically induce cell death via synergistic PTT/TDT, ignoring tumor hypoxia. Moreover, these carrier-free nano-theranostic agents present satisfactory biocompatibility, which could be employed as a powerful weapon to hit hypoxic tumors via MRI-guided oxygen-independent PTT and photonic TDT.

摘要

用于癌症治疗的成像引导光热疗法(PTT)/光动力疗法(PDT)有利于恶性病变的精确定位以及在根除顽固的耐热癌细胞中多种细胞杀伤机制的联合作用。然而,克服肿瘤缺氧对PDT疗效的不利影响仍然是一项挑战。在此,开发了用于磁共振成像(MRI)引导的协同PTT/热动力疗法(TDT)的无载体纳米诊疗剂(AIBME@IR780-APM NPs)。合成了两种IR780衍生物作为纳米药物的主体,赋予纳米药物优势,这是通过两亲性IR780-PEG增强空间稳定性并降低被网状内皮系统摄取的风险,以及IR780-ATU螯合锰用于T加权MRI实现的。2,2'-偶氮二(2-甲基丙酸)二甲酯(AIBME)作为热可分解自由基引发剂,被进一步引入纳米系统,目的是在808 nm激光照射下由IR780引发的PTT过程中产生高细胞毒性的烷基自由基。因此,依次产生的热和烷基自由基通过协同PTT/TDT协同诱导细胞死亡,而忽略肿瘤缺氧。此外,这些无载体纳米诊疗剂具有令人满意的生物相容性,可作为一种强大武器,通过MRI引导的不依赖氧气的PTT和光子TDT来攻击缺氧肿瘤。

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