title: A Targeted DNAzyme-Nanocomposite Probe Equipped with Built-in Zn(2+) Arsenal for Combined Treatment of Gene Regulation and Drug Delivery.
abstract: As catalytic nucleic acids, DNAzymes have been extensively used in the design of sensing platforms. However, their potentials as intelligent drug carriers for responsive drug release in gene therapy and chemotherapy were rarely explored. Herein, we report a dual-functional probe composed of gold nanoparticles (GNPs), catalytic Zn(2+)-dependent DNAzyme, anticancer drug doxorubicin (Dox), targeted AS1411 aptamer and acid-decomposable ZnO quantum dots (ZnO QDs) to achieve intracellular gene regulation and drug delivery in a controlled manner. By means of aptamer-guided targeting and receptor-mediated endocytosis, the probes were specifically internalized into the HeLa cells and trapped in the acidic endo-/lysosomes, where the ZnO QDs as the built-in Zn(2+) arsenal were promptly dissolved to offer Zn(2+), leading to the activation of DNAzyme to cleave the substrate strands, and subsequent drug release. Meanwhile, as designed, one part of the cleaved substrate, hybridized with the overexpressed miR-21 in the target cells, thereby declining its intracellular level. Taken together, the down-regulation of miR-21 has a synergistic effect with Dox to efficiently eradicate the cancer cells. Thus, the favorable biocompatibility, cancer cell specificity and combined treatment make the probe promising for therapy of multidrug-resistant cancer and in vivo application.
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry &Chemical Engineering, Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Zhi-Mei
authors.initials: ZM
authors.lastname: He
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry &Chemical Engineering, Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210023, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry &Chemical Engineering, Nanjing University, Nanjing 210093, P.R. China.|School of Chemistry and Life Science, Nanjing University Jinling College, Nanjing 210089, China.
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry &Chemical Engineering, Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D052157:Aptamers, Nucleotide; D021881:DNA, Catalytic / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism*; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D053761:Nanocomposites; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D015034:Zinc Oxide / Q000378:metabolism*
chemical_list: C513936:AGRO 100; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D021881:DNA, Catalytic; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D004317:Doxorubicin; D015034:Zinc Oxide