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用于肿瘤光热增强铁死亡治疗的高穿透性载药纳米马达

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor.

作者信息

Zhang Yawen, Zhang Ke, Yang Hongna, Hao Yijie, Zhang Jinzha, Zhao Wenbo, Zhang Shirong, Ma Shenglin, Mao Chun

机构信息

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, Jiangsu 210023, China.

Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310006, China.

出版信息

ACS Appl Mater Interfaces. 2023 Mar 22;15(11):14099-14110. doi: 10.1021/acsami.3c00297. Epub 2023 Mar 8.

Abstract

A kind of drug-loaded nanomotors with deep penetration was developed to improve the therapeutic effect of ferroptosis on tumor. The nanomotors were constructed by co-loading hemin and ferrocene (Fc) on the surface of bowl-shaped polydopamine (PDA) nanoparticles. The near-infrared response of PDA makes the nanomotor have high tumor penetration capability. experiments show that the nanomotors can exhibit good biocompatibility, high light to heat conversion efficiency, and deep tumor permeability. It is worth noting that under the catalysis of HO overexpressed in the tumor microenvironment, the Fenton-like reagents hemin and Fc loaded on the nanomotors can increase the concentration of toxic •OH. Furthermore, hemin can consume glutathione in tumor cells and trigger the up-regulation of heme oxygenase-1, which can efficiently decompose hemin to Fe, thus producing the Fenton reaction and causing a ferroptosis effect. Notably, thanks to the photothermal effect of PDA, it can enhance the generation of reactive oxygen species and thus intervene in the Fenton reaction process, thereby enhancing the ferroptosis effect photothermally. antitumor results show that the drug-loaded nanomotors with high penetrability showed an effective antitumor therapeutic effect.

摘要

为提高铁死亡对肿瘤的治疗效果,研发了一种具有深度穿透能力的载药纳米马达。通过将血红素和二茂铁(Fc)共负载在碗状聚多巴胺(PDA)纳米颗粒表面构建纳米马达。PDA的近红外响应使纳米马达具有高肿瘤穿透能力。实验表明,纳米马达具有良好的生物相容性、高光热转换效率和深部肿瘤渗透性。值得注意的是,在肿瘤微环境中过表达的HO催化下,负载在纳米马达上的类芬顿试剂血红素和Fc可增加有毒•OH的浓度。此外,血红素可消耗肿瘤细胞中的谷胱甘肽并触发血红素加氧酶-1的上调,其可将血红素有效分解为Fe,从而产生芬顿反应并引起铁死亡效应。值得注意的是,由于PDA的光热效应,其可增强活性氧的产生,从而干预芬顿反应过程,进而光热增强铁死亡效应。抗肿瘤结果表明,具有高穿透性的载药纳米马达显示出有效的抗肿瘤治疗效果。

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