Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self‐Synergistic Tumor Targeting Therapy |
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Authors: | Wei‐Hai Chen Guo‐Feng Luo Wen‐Xiu Qiu Qi Lei Sheng Hong Shi‐Bo Wang Di‐Wei Zheng Cheng‐Hui Zhu Xuan Zeng Jun Feng Si‐Xue Cheng Xian‐Zheng Zhang |
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Affiliation: | 1. Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, China;2. The Institute for Advanced Studies, Wuhan University, Wuhan, China |
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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. |
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Keywords: | cascade reaction targeted therapies self‐synergistic therapy tumor targeting |
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