title: Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self-Synergistic Tumor Targeting Therapy.
abstract: In this work, a ZnO based nanococktail with programmed functions is designed and synthesized for self-synergistic tumor targeting therapy. The nanococktail can actively target tumors via specific interaction of hyaluronic acid (HA) with CD44 receptors and respond to HAase-rich tumor microenvironment to induce intracellular cascade reaction for controlled therapy. The exposed cell-penetrating peptide (R8) potentiates the cellular uptake of therapeutic nanoparticles into targeted tumor cells. Then ZnO cocktail will readily degrade in acidic endo/lysosomes and induce the production of desired reactive oxygen species (ROS) in situ. The destructive ROS not only leads to serious cell damage but also triggers the on-demand drug release for precise chemotherapy, thus achieving enhanced antitumor efficiency synergistically. After tail vein injection of ZnO cocktail, a favorable tumor apoptosis rate (71.2 ± 8.2%) is detected, which is significantly superior to that of free drug, doxorubicin (12.9 ± 5.2%). Both in vitro and in vivo studies demonstrate that the tailor-made ZnO cocktail with favorable biocompatibility, promising tumor specificity, and self-synergistically therapeutic capacity opens new avenues for cancer therapy.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Wei-Hai
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Wen-Xiu
authors.initials: WX
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Hong
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Shi-Bo
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Di-Wei
authors.initials: DW
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Si-Xue
authors.initials: SX
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, China.|The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D004317:Doxorubicin
keywords: cascade reaction; self-synergistic therapy; targeted therapies; tumor targeting