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

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.

Controlling the transverse proton relaxivity of magnetic graphene oxide

“…The results, in Fig. 7, show that the MGOs have high biocompatibility, in general, which is consonant with previous reports 23,24 . The fact that MGO 3 has the highest relaxivity and remains nontoxic at least up to 2 mM of [Fe] is very promising for contrast agent applications, notwithstanding the fact they have lower relaxivities than SPIOs 28,29 and would require higher concentrations.…”

“…In pursuit of high-performance MRI CAs, the surface modification of IO is mostly executed in the form of core-shell 18,19 and Janus structure 20 using polymer stabilizers along with their controlled shape and size. In addition, with the advances in the research of graphene-based materials, GO has been utilized for surface modification of IO owing to its oxygenated functionalities, i.e., epoxide, hydroxyl, carbonyl, and carboxyl moieties 21,22 and biocompatibility 23,24 . These functionalities can serve as the conjugation sites for IO to form GO-based nanocomposites, and in particular, magnetic graphene oxide (MGO).…”

Evaluation of the Cytotoxicity and Oxidative Stress Response of CeO2-RGO Nanocomposites in Human Lung Epithelial A549 Cells

“…The improved optoelectronic properties of these nanocomposites make them substantial candidates for tissue imaging, biosensing, and targeted drug delivery. Diaz-Diestra et al [24] prepared non-toxic folic acid functionalized RGO/ZnS:Mn nanocomposites that show potential to be used as a platform for targeted cancer treatment. Hence, it is necessary to thoroughly examine the biological interaction of these graphene-based nanocomposites before their applications in nanomedicine and environmental remediation.…”

rGO nanomaterial-mediated cancer targeting and photothermal therapy in a microfluidic co-culture platform

“…2c). While the spectrum of rGO-PEG did not show any absorption peak, rGO-PEG-FA showed the additional peak at 280 nm, which was distinctive in FA [63,64]. This result supported that FA molecules were grafted on rGO surface with PEG.…”