The Use of TAT Peptide-Functionalized Graphene as a Highly Nuclear-Targeting Carrier System for Suppression of Choroidal Melanoma

Abstract

Tumorous metastasis is a difficult challenge to resolve for researchers and for clinicians. Targeted delivery of antitumor drugs towards tumor cells’ nuclei can be a practical approach to resolving this issue. This work describes an efficient nuclear-targeting delivery system prepared from trans-activating transcriptional activator (TAT) peptide-functionalized graphene nanocarriers. The TAT peptide, originally observed in a human immunodeficiency virus 1 (HIV-1), was incorporated with graphene via an edge-functionalized ball-milling method developed by the author’s research group. High tumor-targeting capability of the resulting nanocarrier was realized by the strong affinity between TAT and the nuclei of cancer cells, along with the enhanced permeability and retention (EPR) effect of two-dimensional graphene nanosheets. Subsequently, a common antitumor drug, mitomycin C (MMC), was covalently linked to the TAT-functionalized graphene (TG) to form a nuclear-targeted nanodrug MMC-TG. The presence of nanomaterials inside the nuclei of ocular choroidal melanoma (OCM-1) cells was shown using transmission electron microscopy (TEM) and confocal laser scanning microscopy. In vitro results from a Transwell co-culture system showed that most of the MMC-TG nanodrugs were delivered in a targeted manner to the tumorous OCM-1 cells, while a very small amount of MMC-TG was delivered in a non-targeted manner to normal human retinal pigment epithelial (ARPE-19) cells. TEM results further confirmed that apoptosis of OCM-1 cells was started from the lysis of nuclear substances, followed by the disappearance of nuclear membrane and cytoplasm. This suggests that the as-synthesized MMC-TG is a promising nuclear-target nanodrugfor resolution of tumorous metastasis issues at the headstream.

Gelatin-Graphene Oxide Nanocomposite Hydrogels for Kluyveromyces lactis Encapsulation: Potential Applications in Probiotics and Bioreactor Packings

“…Much progress has been made to achieve specific delivery goals regarding selectivity, bioavailability, and guided transport and targeting [44][45][46]. For instance, carbon-based nanomaterials such as graphene oxide, reduced graphene oxide, graphene quantum dots, graphene nanoribbons, silica-based nanocarriers, and inorganic nanoparticles [42,43,47,48] have been used to infiltrate tumors with the aid of cell-penetrating agents, and due to enhanced permeation and retention (EPR) mechanisms, they remain inside them for a more extended period [49][50][51].…”

A novel Vancomycin‐Functionalized‐Magnetic Graphene Composite for Use as a Near‐Infrared‐Induced Synergistic Chemo‐Photothermal Antibacterial

“…Cytotoxicity of MCG and VCM-MCG: Human RPE cellswere tested as a normal cell control to evaluate the cytotoxicity of nanomaterials in vitro. [37] A typical cell line (ARPE-19) of RPE cells was tested. ARPE-19 cells were cultured at a density of 1 × 10 4 cells per well with various amounts of nanomaterials in a humidified atmosphere (5% CO 2 and 95% O 2 ) at 37°C for 24 h. A cell counting kit-8 (CCK-8) was used to calculate cell viability.…”

Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy

“…Nanoparticles also offer the ability for ligand attachment, which can enhance corneal permeation [ 45 , 46 , 47 , 48 ]. Moreover, the use of modified nanoparticles for tissue-specific penetration and prevention of degradation of therapeutic agents by more effective routes of delivery, could help develop nonviral vectors with highly efficient transfection activity to the target tissues/cells [ 35 , 49 ]. The positive charge and hydrophobicity characteristic of most drugs is associated with decreased intravitreal mobility.…”