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Nanomaterials 2018, 8(7), 484; https://doi.org/10.3390/nano8070484

Graphene Oxide/ZnS:Mn Nanocomposite Functionalized with Folic Acid as a Nontoxic and Effective Theranostic Platform for Breast Cancer Treatment

1
Molecular Sciences Research Center, University of Puerto Rico, San Juan, PR 00926, USA
2
Department of Chemistry, University of Puerto Rico, San Juan, PR 00925-2534, USA
3
Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
4
Department of Physics, University of Puerto Rico, San Juan, PR 00925-2537, USA
5
Department of Biology, University of Puerto Rico, San Juan, PR 00925-2537, USA
*
Authors to whom correspondence should be addressed.
Received: 6 June 2018 / Revised: 20 June 2018 / Accepted: 26 June 2018 / Published: 30 June 2018
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Abstract

Nanoparticle-based cancer theranostic agents generally suffer of poor dispersability in biological media, re-agglomeration over time, and toxicity concerns. To address these challenges, we developed a nanocomposite consisting of chemically-reduced graphene oxide combined with manganese-doped zinc sulfide quantum dots and functionalized with folic acid (FA-rGO/ZnS:Mn). We studied the dispersion stability, Doxorubicin (DOX) loading and release efficiency, target specificity, internalization, and biocompatibility of FA-rGO/ZnS:Mn against folate-rich breast cancer cells, and compared to its uncoated counterpart (rGO/ZnS:Mn). The results indicate that DOX is adsorbed on the graphene surface via π–π stacking and hydrophobic interaction, with enhanced loading (~35%) and entrapment (~60%) efficiency that are associated to the chelation of DOX and surface Zn2+ ions. DOX release is favored under acidic conditions reaching a release of up to 95% after 70 h. Membrane integrity of the cells assessed by Lactate dehydrogenase (LDH) release indicate that the surface passivation caused by folic acid (FA) functionalization decreases the strong hydrophobic interaction between the cell membrane wall and the edges/corners of graphene flakes. Chemotherapeutic effect assays reveal that the cancer cell viability was reduced up to ~50% at 3 µg/mL of DOX-FA-rGO/ZnS:Mn exposure, which is more pronounced than those obtained for free DOX at the same doses. Moreover, DOX-rGO/ZnS:Mn did not show any signs of toxicity. An opposite trend was observed for cells that do not overexpress the folate receptors, indicating that FA functionalization endows rGO/ZnS:Mn with an effective ability to discriminate positive folate receptor cancerous cells, enhancing its drug loading/release efficiency as a compact drug delivery system (DDS). This study paves the way for the potential use of functionalized rGO/ZnS:Mn nanocomposite as a platform for targeted cancer treatment. View Full-Text
Keywords: drug delivery; quantum dots; reduced graphene oxide; chemotherapy; theranostics drug delivery; quantum dots; reduced graphene oxide; chemotherapy; theranostics
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Diaz-Diestra, D.; Thapa, B.; Badillo-Diaz, D.; Beltran-Huarac, J.; Morell, G.; Weiner, B.R. Graphene Oxide/ZnS:Mn Nanocomposite Functionalized with Folic Acid as a Nontoxic and Effective Theranostic Platform for Breast Cancer Treatment. Nanomaterials 2018, 8, 484.

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