首页|MnO2-coated nanodiamond-driven photodynamic therapy for enhanced antitumor effect by addressing hypoxia and glutathione depletion

MnO2-coated nanodiamond-driven photodynamic therapy for enhanced antitumor effect by addressing hypoxia and glutathione depletion

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The generation of reactive oxygen species(ROS)at the tumor site to induce destruction is emerging as a novel strategy for cancer treatment,which involves photodynamic therapy(PDT).Nevertheless,tumors typically create a hypoxic environment and are equipped with an endogenous antioxidant defense system that could potentially impede the efficiency of the therapeutic approach.To overcome these drawbacks,herein,a tumor microenvironment-responsive the ND-PAA-CD-Ce6@MnO2(NPCC@M)de-livery system was fabricated by disulfide bond coupling chlorin e6(Ce6)to nanodiamond(ND)and further wrapped by MnO2 nanosheets to facilitate PDT.The use of disulfide bond not only stabilizes Ce6 in the blood circulation to prevent premature leakage,but also destroys the antioxidant barrier of overexpressed glutathione(GSH)in tumor cells.Moreover,the outer MnO2 was rapidly degraded by the endogenous hydrogen peroxide(H2O2)in the acidic pH and GSH within the tumor cells,which leads to an abundance of O2 and while increases the level of 1O2 under laser irradiation.The results eventually broke the redox homeostasis and attenuate hypoxia,thereby inducing apoptosis and necrosis of tumor cells.Detailed in vitro and in vivo biological effect has revealed a good biosafety profile and a high tumor suppression effect.Such a novel ND-based system with tumor microenvironment-modulating capability to elevate oxygen content and promote GSH consumption in tumor cells opens new opportunities for enhanced ROS treatment paradigms.

NanodiamondPhotodynamicChlorin e6MnO2Tumor suppression

Jicheng Cui、Dongmei Zhang、Hui Qiao、Zeyu Yan、Wenxia Zhang、Yingqi Li

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Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Institute of Molecular Science,Shanxi University,Taiyuan,030006,China

Taiyuan Central Hospital,Taiyuan,030009,China

School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan,030006,China

Central Government Guiding Local Science and Technology DevelopmentShanxi Province Natural Science FoundationShanxi Province Patent Transformation ProjectCIRP Open Fund of Radiation Protection LaboratoriesInterdisciplinary Construction Project of Shanxi University

YDZX20191400002477202203021221003202304015CIRP-CAEA20220203113541028

2024

10.1016/j.partic.2024.05.016

颗粒学报(英文版)
中国颗粒学会　中国科学院过程工程研究所

颗粒学报(英文版)

CSTPCD
影响因子：0.632
ISSN：1674-2001
年,卷(期)：2024.92(9)