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莫能菌素增强的细胞外囊泡的生成作为转胞体促进融合脂质体中焦脱镁叶绿酸-a 向肿瘤的穿透

Monensin Enhanced Generation of Extracellular Vesicles as Transfersomes for Promoting Tumor Penetration of Pyropheophorbide-a from Fusogenic Liposome.

机构信息

Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P. R. China.

University of Chinese Academy of Sciences, Beijing 100864, P. R. China.

出版信息

Nano Lett. 2022 Feb 9;22(3):1415-1424. doi: 10.1021/acs.nanolett.1c04962. Epub 2022 Jan 24.

Abstract

The current state of antitumor nanomedicines is severely restricted by poor penetration in solid tumors. It is indicated that extracellular vesicles (EVs) secreted by tumor cells can mediate the intercellular transport of antitumor drug molecules in the tumor microenvironment. However, the inefficient generation of EVs inhibits the application of this approach. Herein, we construct an EV-mediated self-propelled liposome containing monensin as the EV secretion stimulant and photosensitizer pyropheophorbide-a (PPa) as a therapeutic agent. Monensin and PPa are first transferred to the tumor plasma membrane with the help of membrane fusogenic liposomes. By hitchhiking EVs secreted by the outer tumor cells, both drugs are layer-by-layer transferred into the deep region of a solid tumor. Particularly, monensin, serving as a sustainable booster, significantly amplifies the EV-mediated PPa penetration by stimulating EV production. Our results show that this endogenous EV-driven nanoplatform leads to deep tumor penetration and enhanced phototherapeutic efficacy.

摘要

当前抗肿瘤纳米药物的发展受到实体瘤内穿透性差的严重限制。有研究表明,肿瘤细胞分泌的细胞外囊泡(EVs)可以在肿瘤微环境中介导抗肿瘤药物分子的细胞间转运。然而,EVs 的生成效率低下限制了这种方法的应用。在此,我们构建了一种 EV 介导体自主推进脂质体,其中包含作为 EV 分泌刺激物的莫能菌素和作为治疗剂的光热剂原卟啉钠(PPa)。莫能菌素和 PPa 首先在膜融合脂质体的帮助下转移到肿瘤质膜上。通过搭乘由外肿瘤细胞分泌的 EV,两种药物都被层层转移到实体瘤的深部区域。特别是,莫能菌素作为一种可持续的助推剂,通过刺激 EV 的产生,显著放大了 EV 介导的 PPa 穿透。我们的结果表明,这种内源性 EV 驱动的纳米平台可实现肿瘤的深层穿透并增强光疗效果。

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