title: Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy.
abstract: Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of the Cumberlands, 7000 College Station Drive, Williamsburg, KY 40769, USA.
authors.forename: Zheran
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Bai
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Jianqi
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Dongkai
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. wangycsyphu@126.com pharm305@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D017209:Apoptosis; D002138:Calibration; D002244:Carbon / Q000737:chemistry*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004578:Electron Spin Resonance Spectroscopy; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy; D055095:Optics and Photonics; D021382:Protein Sorting Signals; D045663:Quantum Dots; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000903:Antibiotics, Antineoplastic; D006835:Hydrazones; D021382:Protein Sorting Signals; D002244:Carbon; D004317:Doxorubicin