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

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Abstract

Design of powerful nanosystems to overcome multidrug resistance (MDR) for effective chemotherapy of cancer currently remains a great challenge. Herein, we report the development of a poly(amidoamine) (PAMAM) dendrimer/carbon dot nanohybrid for dual drug loading to overcome MDR and simultaneously monitor cancer cells via fluorescence imaging. First, blue-emitting carbon dots (CDs) were synthesized using sodium citrate as a carbon source via the hydrothermal method and used as a carrier to load the anticancer drug doxorubicin (DOX) through non-covalent interactions, thus forming CDs/DOX complexes. In parallel, PAMAM dendrimers of generation 5 (G5) were covalently modified by the 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 showed that the nanohybrids possessed good colloidal stability and enabled significant inhibition of cancer cells due to the presence of TPGS, which can inhibit P-glycoprotein (P-gp) by decreasing ATP levels and increasing ROS levels; simultaneously, fluorescence imaging of cancer cells could be achieved in vitro due to the luminescence of CDs. In addition, the attached RGD ligands rendered 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.

Graphical abstract: Design of dual drug-loaded dendrimer/carbon dot nanohybrids for fluorescence imaging and enhanced chemotherapy 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, 2019, Advance Article
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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, 2019, Advance Article , DOI: 10.1039/C8TB02723D

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