Dual Intratumoral Redox/Enzyme-Responsive NO-Releasing Nanomedicine for the Specific, High-Efficacy, and Low-Toxic Cancer Therapy

被引:219
作者
Jia, Xiaobo [1 ]
Zhang, Yihua [2 ]
Zou, Yu [2 ]
Wang, Yao [1 ]
Niu, Dechao [1 ]
He, Qianjun [3 ]
Huang, Zhangjian [2 ]
Zhu, Weihong [4 ,5 ]
Tian, He [4 ,5 ]
Shi, Jianlin [1 ]
Li, Yongsheng [1 ]
机构
[1] East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Lab Low Dimens Mat Chem,Minist Educ, Shanghai 200237, Peoples R China
[2] China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
[3] Shenzhen Univ, Hlth Sci Ctr, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China
[4] East China Univ Sci & Technol, Key Lab Adv Mat, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China
[5] East China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China
基金
中国国家自然科学基金;
关键词
dual-responsiveness; nitric oxide; prodrug delivery; safe treatment; tumor therapy; DRUG-DELIVERY; BREAST-CANCER; NITRIC-OXIDE; MACROMOLECULAR THERAPEUTICS; CARCINOMA ACTIVITY; OLEANOLIC ACID; MICELLES; DESIGN; NANOPARTICLES; CHEMOTHERAPY;
D O I
10.1002/adma.201704490
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Chemotherapy suffers numbers of limitations including poor drug solubility, nonspecific biodistribution, and inevitable adverse effects on normal tissues. Tumor-targeted delivery and intratumoral stimuli-responsive release of drugs by nanomedicines are considered to be highly promising in solving these problems. Compared with traditional chemotherapeutic drugs, high concentration of nitric oxide (NO) exhibits unique anticancer effects. The development of tumor-targeting and intratumoral microenvironment-responsive NO-releasing nanomedicines is highly desired. Here a novel kind of organic-inorganic composite nanomedicine (QM-NPQ@PDHNs) is presented by encapsulating a glutathione S-transferases (GST)-responsive drug O-2-(2,4-dinitro-5-{[2-(-d-galactopyranosyl olean-12-en-28-oate-3-yl)-oxy-2-oxoethyl] piperazine-1-yl} phenyl) 1-(methylethanolamino)diazen-1-ium-1,2-dilate (NPQ) as NO donor and an aggregation-induced-emission (AIE) red fluorogen QM-2 into the cores of the hybrid nanomicelles (PEGylated disulfide-doped hybrid nanocarriers (PDHNs)) with glutathione (GSH)-responsive shells. The QM-NPQ@PDHN nanomedicine is able to respond to the intratumoral over-expressed GSH and GST, resulting in the responsive biodegradation of the protective organosilica shell and NPQ release, and subsequent NO release within the tumor, respectively, and thus normal organs remain unaffected. This work demonstrates a paradigm of dual intratumoral redox/enzyme-responsive NO-release nanomedicine for tumor-specific and high-efficacy cancer therapy.
引用
收藏
页数:9
相关论文
共 52 条
  • [11] Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures
    Ding, Yanping
    Su, Shishuai
    Zhang, Ruirui
    Shao, Leihou
    Zhang, Yinlong
    Wang, Bin
    Li, Yiye
    Chen, Long
    Yu, Qun
    Wu, Yan
    Nie, Guangjun
    [J]. BIOMATERIALS, 2017, 113 : 243 - 252
  • [12] pH-responsive complexes using prefunctionalized polymers for synchronous delivery of doxorubicin and siRNA to cancer cells
    Dong, Da-Wen
    Xiang, Bai
    Gao, Wei
    Yang, Zhen-Zhen
    Li, Jing-Quan
    Qi, Xian-Rong
    [J]. BIOMATERIALS, 2013, 34 (20) : 4849 - 4859
  • [13] El S. S., 2015, ORG BIOMOL CHEM, V13, P1017
  • [14] Disulfide-functional poly(amido amine)s with tunable degradability for gene delivery
    Elzes, M. Rachel
    Akeroyd, Niels
    Engbersen, Johan F. J.
    Paulusse, Jos M. J.
    [J]. JOURNAL OF CONTROLLED RELEASE, 2016, 244 : 357 - 365
  • [15] Hybrid Molecule from O2-(2,4-Dinitrophenyl)diazeniumdiolate and Oleanolic Acid: A Glutathione S-Transferase π-Activated Nitric Oxide Prodrug with Selective Anti-Human Hepatocellular Carcinoma Activity and Improved Stability
    Fu, Junjie
    Liu, Ling
    Huang, Zhangjian
    Lai, Yisheng
    Ji, Hui
    Peng, Sixun
    Tian, Jide
    Zhang, Yihua
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (11) : 4641 - 4655
  • [16] The role of nitric oxide in tumour progression
    Fukumura, Dai
    Kashiwagi, Satoshi
    Jain, Rakesh K.
    [J]. NATURE REVIEWS CANCER, 2006, 6 (07) : 521 - 534
  • [17] Acid-cleavable ketal containing poly(β-amino ester) for enhanced siRNA delivery
    Guk, Kyeonghye
    Lim, Hyungsuk
    Kim, Byungkuk
    Hong, Minsung
    Khang, Gilson
    Lee, Dongwon
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2013, 453 (02) : 541 - 550
  • [18] Synergistic gene and drug tumor therapy using a chimeric peptide
    Han, Kai
    Chen, Si
    Chen, Wei-Hai
    Lei, Qi
    Liu, Yun
    Zhuo, Ren-Xi
    Zhang, Xian-Zheng
    [J]. BIOMATERIALS, 2013, 34 (19) : 4680 - 4689
  • [19] One-Pot Synthesis of Dual Stimulus-Responsive Degradable Hollow Hybrid Nanoparticles for Image-Guided Trimodal Therapy
    Hayashi, Koichiro
    Maruhashi, Takuma
    Nakamura, Michihiro
    Sakamoto, Wataru
    Yogo, Toshinobu
    [J]. ADVANCED FUNCTIONAL MATERIALS, 2016, 26 (47) : 8613 - 8622
  • [20] Polyprodrug Amphiphiles: Hierarchical Assemblies for Shape-Regulated Cellular Internalization, Trafficking, and Drug Delivery
    Hu, Xianglong
    Hu, Jinming
    Tian, Jie
    Ge, Zhishen
    Zhang, Guoying
    Luo, Kaifu
    Liu, Shiyong
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (46) : 17617 - 17629