A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy

Abstract

The design of multifunctional materials able to both selectively deliver a drug into cells in a targeted manner and display an enhanced propensity for biodegradation is an important goal. Here, graphene oxide (GO) is functionalized with the chemotactic peptide N-formyl-methionyl-leucylphenylalanine (fMLP) known to interact with the formyl peptide receptor, which is expressed in different cancer cells, including cervical carcinoma cells. This study highlights the ability of GOfMLP for targeted drug delivery and cancer cell killing and the subsequent degradation capacity of the hybrid. Biodegradation is assessed via Raman spectroscopy and transmission electron microscopy. The results show that GOfMLP is susceptible to faster myeloperoxidase-mediated degradation. The hybrid material, but not GO, is capable of inducing neutrophil degranulation with subsequent degradation, being the first study showing inducible neutrophil degradation by the nanomaterial itself with no prior activation of the cells. In addition, confocal imaging and flow cytometry using HeLa cells demonstrate that GOfMLP is able to deliver the chemotherapeutic agent doxorubicin faster into cells, inducing higher levels of apoptosis, when compared to nonfunctionalized GO. The results reveal that GOfMLP is a promising carrier able to efficiently deliver anticancer drugs, being endowed with the ability to induce its own biodegradation.

Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract

“…3 Furthermore, we demonstrated in a previous study that primary human neutrophils are capable of degrading GO when activated to undergo degranulation with release of MPO, 4 while GO functionalized with a chemotactic peptide triggered neutrophil activation with subsequent degradation of GO. 5 Single-and few-layer graphene is also susceptible to enzymatic degradation though the process was found to be less efficient as compared to GO. 6 Previous studies on single-and multi-walled carbon nanotubes (CNTs) have revealed the propensity of these materials to undergo peroxidase-mediated biodegradation.…”

Efficacy, Biocompatibility and Degradability of Carbon Nanoparticles for Photothermal Therapy of Lung Cancer

“…To obtain human monocyte-derived macrophages (HMDMs), CD14 + monocytes were cultured in RPMI-1640 cell medium supplemented with 2mM l-glutamine, 100 IU/ml penicillin, 100 μg/ml streptomycin and 10% heat-inactivated FBS, supplemented with 50 ng/ml recombinant macrophage colony-stimulating factor (M-CSF) (R&D Systems, MN, USA) for 3 days. Peripheral blood neutrophils (PMNs) were isolated from buffy coats as previously described [29]. Briefly, neutrophils were isolated by density gradient centrifugation using Lymphoprep™ followed by gradient sedimentation in a 5% dextran solution and hypotonic lysis of residual erythrocytes.…”

“…Freshly isolated HMDMs and PMNs were seeded in 96-well plates in phenol red-free RPMI-1640 cell medium at a density of 10 6 cells/ml and exposed to CNPs at the indicated concentrations or were maintained in cell medium alone (negative control). The alamarBlue™ assay (Thermo Scientific, Göteborg, Sweden) was performed for cytotoxicity assessment of the PMNs and HMDMs as described previously [29]. Briefly, following exposure to CNPs, a 10% (v/v) solution of alamarBlue reagent was added to each well.…”

“…Neutrophils were assessed for degranulation by flow cytometric analysis, as described before [29]. Briefly, externalized MPO was detected by fluorescein isothiocyanate (FITC)-labeled antibody according to the manufacturer's instructions for the FITC anti-human flow kit (Biolegend, CA, USA).…”

Degradation of Structurally Defined Graphene Nanoribbons by Myeloperoxidase and the Photo‐Fenton Reaction

“…In recent years, graphene and its derivatives have been widely studied in the fields of medicine and gene delivery, bioimaging, biodetection, immune‐modulation and cancer treatment . As an emerging member in the graphene family, structurally well‐defined graphene nanoribbons (GNRs) have attracted enormous attention due to their controllable structures including length, width and edges .…”