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具有同时光热/抗炎活性以预防乳腺癌转移的胭脂红酸/铁离子自组装多酶模拟纳米药物。

Carminic acid/ferric ion self assembled multienzyme mimetic nanodrug with concurrent photothermal/anti-inflammatory activity to prevent breast cancer metastasis.

作者信息

Wang Mingcheng, Yi Huixi, Zheng Qibao, Younis Muhammad Adnan, Guo Liyou, Zhan Zhixiong, Younis Muhammad Rizwan, Jin Chengzhi, Zhang Dong-Yang

机构信息

Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital and School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China.

Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, CA, 90095, United States.

出版信息

Mater Today Bio. 2025 Jun 28;33:102028. doi: 10.1016/j.mtbio.2025.102028. eCollection 2025 Aug.

Abstract

The high metastatic rate of breast tumor is the prominent reason of its poor prognosis, while the inflammatory microenvironment of tumor tissues further promoted tumor metastasis. Although photothermal therapy (PTT) displays high antitumor efficacy, the rise of inflammation-induced reactive oxygen species (ROS) during PTT exacerbate tumor metastasis. To prevent breast tumor metastasis and relieve inflammation-induced oxidative stress during PTT, herein, we developed self-assembled nanodrugs (FCP) consisting of carminic acid, iron ion, and polyvinylpyrrolidone, demonstrating photoacoustic imaging-guided PTT and anti-inflammatory activity to restrict the growth of both primary breast tumor and metastatic tumor. The as designed self-assembled spherical FCP nanoparticles (NPs, 41 nm) exhibited good light to heat conversion and broad-spectrum multienzyme (superoxide dismutase, etc.) mimetic activity to scavenge excess ROS and alleviate oxidative stress. Meanwhile, FCP NPs showed a positive correlation between the photothermal heating and ROS scavenging, allowing the continuous consumption of ROS during PTT. Importantly, owing to the intrinsic bimodal photothermal and photoacoustic imaging abilities, FCP NPs effectively guided and monitored the treatment process, which facilitated to restrict the growth of both primary and metastatic breast tumor due to coordinated PTT and anti-inflammation as confirmed by TUNEL, ki67, and matrix metalloproteinase-9 stainings. Whereas FCP NPs did not pose any potential damage to the vital organs, presenting good biosafety . We envision that self-assembled nanodrugs with concurrent anti-inflammatory and photothermal activities may have great clinical prospects in the treatment of metastatic cancers.

摘要

乳腺肿瘤的高转移率是其预后不良的主要原因,而肿瘤组织的炎性微环境进一步促进了肿瘤转移。尽管光热疗法(PTT)显示出较高的抗肿瘤疗效,但PTT过程中炎症诱导的活性氧(ROS)的增加会加剧肿瘤转移。为了在PTT期间预防乳腺肿瘤转移并减轻炎症诱导的氧化应激,在此,我们开发了由胭脂红酸、铁离子和聚乙烯吡咯烷酮组成的自组装纳米药物(FCP),其具有光声成像引导的PTT和抗炎活性,可抑制原发性乳腺肿瘤和转移性肿瘤的生长。所设计的自组装球形FCP纳米颗粒(NPs,41 nm)表现出良好的光热转换性能和广谱多酶(超氧化物歧化酶等)模拟活性,以清除过量的ROS并减轻氧化应激。同时,FCP NPs的光热加热与ROS清除之间呈正相关,使得PTT期间ROS能够持续消耗。重要的是,由于其固有的双模态光热和光声成像能力,FCP NPs有效地引导和监测了治疗过程,通过TUNEL、ki67和基质金属蛋白酶-9染色证实,由于协同的PTT和抗炎作用,这有助于抑制原发性和转移性乳腺肿瘤的生长。而FCP NPs对重要器官没有任何潜在损害,具有良好的生物安全性。我们设想,具有同时抗炎和光热活性的自组装纳米药物在转移性癌症的治疗中可能具有巨大的临床前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/318f/12270016/4f3086135f9d/ga1.jpg

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