A Redox-responsive Dihydroartemisinin Dimeric Nanoprodrug for Enhanced Antitumor Activity

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2021 Dec 21

PMID 34930288

Citations 9

Authors

Yawei Li

Qing Pei

Baiji Cui

Hongmei Zhang

Liu Han

Wenqing Li

Wenhe Zhu

Xianmin Feng

Zhigang Xie

Affiliations

Soon will be listed here.

Abstract

Redox-responsive drug delivery system emerges as a hopeful platform for tumor treatment. Dihydroartemisinin (DHA) has been investigated as an innovative tumor therapeutic agent. Herein, a DHA dimeric prodrug bridged with disulfide bond as linker (DHA-SS) has been designed and synthesized. The prepared prodrugs could self-assemble into nanoparticles (SS NPs) with high DHA content (> 90%) and robust stability. These SS NPs display sensitive redox responsive capability and can release DHA under the tumor heterogeneity microenvironment. SS NPs possess preferable antitumor therapeutic activity in contrast with free DHA. Moreover, the possible anti-cancer mechanism of SS NPs was investigated through RNA-seq analysis, bioinformatics and molecular biological method. SS NPs could induce apoptosis via mitochondrial apoptosis pathway, as well as glycolysis inhibition associate with the regulation of PI3K/AKT/HIF-1α signal path, which may offer an underlying therapeutic target for liver cancer. Our study highlights the potential of using redox responsive prodrug nanoparticles to treat cancer, meanwhile provides insights into the anti-cancer mechanism of DHA prodrug.

Citing Articles

Artemisinin and Its Derivatives as Potential Anticancer Agents.

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2-Monoacylglycerol Mimetic Liposomes to Promote Intestinal Lymphatic Transport for Improving Oral Bioavailability of Dihydroartemisinin.

Zheng B, Pan F, Shi M, He C, He B, Wang R Int J Nanomedicine. 2024; 19:5273-5295.

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Nanoscale dihydroartemisinin@zeolitic imidazolate frameworks for enhanced antigiardial activity and mechanism analysis.

Jiang X, Li Y, Liu S, Sun H, Zheng M, Wan X Front Vet Sci. 2024; 11:1364287.

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Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered "valve-off" starvation therapy.

Su X, Ouyang B, Liu Y, Wang Y, Xu R, Niu L Asian J Pharm Sci. 2023; 18(5):100850.

PMID: 37920651 PMC: 10618705. DOI: 10.1016/j.ajps.2023.100850.

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