Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self-Synergistic Tumor Targeting Therapy.
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.
['Chen|Wei-Hai|WH|', 'Luo|Guo-Feng|GF|', 'Qiu|Wen-Xiu|WX|', 'Lei|Qi|Q|', 'Hong|Sheng|S|', 'Wang|Shi-Bo|SB|', 'Zheng|Di-Wei|DW|', 'Zhu|Cheng-Hui|CH|', 'Zeng|Xuan|X|', 'Feng|Jun|J|', 'Cheng|Si-Xue|SX|', 'Zhang|Xian-Zheng|XZ|']
D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D004317:Doxorubicin D005434:Flow Cytometry D006801:Humans D042541:Intracellular Space D008807:Mice, Inbred BALB C D008819:Mice, Nude D053758:Nanoparticles D009369:Neoplasms D017382:Reactive Oxygen Species
cascade reaction tumor targeting targeted therapies self-synergistic therapy