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.
Highlights
According to the US National Cancer Institute, approximately 1.7 million people in the US will be diagnosed with cancer during this year [1]
Among the different nanomaterial-based drug delivery system (DDS) reported to date, those based on quantum dots (QDs) offer superior advantages due to the exotic features of QDs, such as unique tunable optical properties, high quantum yield, photo-stability and broad absorption with relatively-narrow and symmetric emission, and the fact that they can be simultaneously used for bio-imaging cancerous tissues and as photosensitizers in photodynamic therapy (PDT) [9,10,11]
SEM image analysis indicates that the samples consist of particles in the nanoscale that are well dispersed onto the surface of graphene flakes
Summary
According to the US National Cancer Institute, approximately 1.7 million people in the US will be diagnosed with cancer during this year [1]. Among the different nanomaterial-based DDSs reported to date, those based on quantum dots (QDs) offer superior advantages due to the exotic features of QDs, such as unique tunable optical properties, high quantum yield, photo-stability and broad absorption with relatively-narrow and symmetric emission, and the fact that they can be simultaneously used for bio-imaging cancerous tissues and as photosensitizers in photodynamic therapy (PDT) [9,10,11] This technology is limited to the use of DDSs that contain acutely toxic metals (such as cadmium and indium), which might get released from the QDs structure into cellular compartments causing serious toxic effects [12,13,14]. We evaluate the efficiency of this DDS to release DOX at acidic conditions (similar to endosomic pH in cancer cells), and its capability to discriminate positive folate receptor cancer cells
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