MnO_(2)-coated nanodiamond-driven photodynamic therapy for enhanced antitumor effect by addressing hypoxia and glutathione depletion  

作　　者：Jicheng Cui Dongmei Zhang Hui Qiao Zeyu Yan Wenxia Zhang Yingqi Li 

机构地区：[1]Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Institute of Molecular Science,Shanxi University,Taiyuan,030006,China [2]Taiyuan Central Hospital,Taiyuan,030009,China [3]School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan,030006,China

出　　处：《Particuology》2024年第9期305-315,共11页颗粒学报（英文版）

基　　金：the Central Government Guiding Local Science and Technology Development(grant No.YDZX20191400002477);the Shanxi Province Natural Science Foundation(grant No.202203021221003);Shanxi Province Patent Transformation Project(grant No.202304015);CIRP Open Fund of Radiation Protection Laboratories(grant No.CIRP-CAEA20220203);Interdisciplinary Construction Project of Shanxi University(grant No.113541028).

摘　　要：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@MnO_(2)(NPCC@M)delivery system was fabricated by disulfide bond coupling chlorin e6(Ce6)to nanodiamond(ND)and further wrapped by MnO_(2)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 MnO_(2)was rapidly degraded by the endogenous hydrogen peroxide(H_(2)O_(2))in the acidic pH and GSH within the tumor cells,which leads to an abundance of O_(2)and while increases the level of 1O_(2)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.

关 键 词：NANODIAMOND Photodynamic Chlorin e6 MnO_(2) Tumor suppression 

分 类 号：TB383[一般工业技术—材料科学与工程] R730.5[医药卫生—肿瘤]