Co-delivery of Doxorubicin and DNAzyme Using ZnO@polydopamine Core-Shell Nanocomposites for Chemo/Gene/Photothermal Therapy.
Acta Biomaterialia(2020)
摘要
Multi-modal nanomedicines that synergistically combine chemo-, gene-, and photothermal therapy have shown great potential for cancer treatment. In this study, a core-shell nanosystem-based on a zinc oxide (ZnO) nanocore and a polydopamine (PDA) shell was constructed to integrate chemo- (doxorubicin, DOX), gene- (DNAzyme, DZ), and photothermal (PDA layer) therapy in one system. Instead of small interfering RNAs, we employed DZ for tumor-related gene (survivin) regulation owing to its higher stability, biocompatibility, and predictable activity. DOX and amino-modified DZ were loaded onto the PDA shell via physisorption and covalent conjugation, respectively. Specifically, the ZnO nanocore was designed as a metal cofactor reservoir to release Zn2+ in response to intracellular stimuli, which triggered the activation of DZ for gene silencing after endocytosis into cells. Both in vitro and in vivo experiments demonstrated the enhanced anti-tumor efficacy of these multifunctional nanocomposites and highlighted the advantages of these nano-drug delivery systems to alleviate the side effects of DOX. This study provides a strategy for synergistic cancer therapy via chemo/gene/photothermal combination and offers a strategy to harness DZ as a gene-silencing tool for disease treatment in combination with other therapeutic modalities.
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关键词
Nanomedicine,Combination therapy,Cancer,Metal cofactor,Self-activation,Stimuli-responsive
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