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Design of dual drug-loaded dendrimer/carbon dot nanohybrids for fluorescence imaging and enhanced chemotherapy of cancer cells

Abstract

Design of powerful nanosystems to overcome multidrug resistance (MDR) for effective chemotherapy of cancer currently remains to be a great challenge. Herein, we report the development of a poly(amidoamine) (PAMAM) dendrimer/carbon dot nanohybrid for dual drug loading to overcome the MDR and simultaneously for monitoring cancer cells via fluorescence imaging. Firstly, blue-emitting carbon dots (CDs) were synthesized using sodium citrate as a carbon source via a hydrothermal method and used as a carrier to load anticancer drug doxorubicin (DOX) via non-covalent interaction to form CDs/DOX complexes, and in parallel PAMAM dendrimers of generation 5 (G5) were covalently modified with targeting ligand cyclic arginine-glycine-aspartic (RGD) peptide and the drug efflux inhibitor D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). Then, through electrostatic interaction, functional dendrimers (G5-RGD-TPGS) were complexed with CDs/DOX complexes to form a dual drug-loaded nanohybrid system. The dual drug-loaded dendrimer/CD nanohybrids were well characterized. We show that the nanohybrids possess good colloidal stability, enable significant inhibition of cancer cells due to the presence of TPGS that can inhibit P-glycoprotein (P-gp) by decreasing ATP level and increasing ROS level, and simultaneously achieve fluorescence imaging of cancer cells in vitro due to the luminescence of CDs. In addition, the attached RGD ligands render the nanohybrid with targeting specificity to cancer cells expressing αvβ3 integrin receptors. The developed dual drug-loaded dendrimer/CD nanohybrid may be used as a promising theranostic platform to overcome MDR for enhanced chemotherapy as well as for fluorescence imaging of cancer cells.

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Publication details

The article was received on 15 Oct 2018, accepted on 27 Nov 2018 and first published on 29 Nov 2018


Article type: Paper
DOI: 10.1039/C8TB02723D
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Design of dual drug-loaded dendrimer/carbon dot nanohybrids for fluorescence imaging and enhanced chemotherapy of cancer cells

    D. Li, Y. Fan, M. Shen, I. Bányai and X. Shi, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB02723D

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