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

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.

The Application of Whole Cell-Based Biosensors for Use in Environmental Analysis and in Medical Diagnostics.

Various whole cell-based biosensors have been reported in the literature for the last 20 years and these reports have shown great potential for their use in the areas of pollution detection in environmental and in biomedical diagnostics. Unlike other reviews of this growing field, this mini-review argues that: (1) the selection of reporter genes and their regulatory proteins are directly linked to the performance of celllular biosensors; (2) broad enhancements in microelectronics and information technologies have also led to improvements in the performance of these sensors; (3) their future potential is most apparent in their use in the areas of medical diagnostics and in environmental monitoring; and (4) currently the most promising work is focused on the better integration of cellular sensors with nano and micro scaled integrated chips. With better integration it may become practical to see these cells used as (5) real-time portable devices for diagnostics at the bedside and for remote environmental toxin detection and this in situ application will make the technology commonplace and thus as unremarkable as other ubiquitous technologies.

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

Antibiotic-resistant bacterial strains are a major cause of disease. They continue to remain a challenge in the clinic particularly in the vision system. For example, infectious endophthalmitis is a major blind-causing disease caused by bacteria. A highly efficient synergistic antibacterial treatment that uses a photothermal antibacterial therapeutic with a chemo-antibacterial therapeutic in a multifunctional nanocomposite is reported. It is prepared by immobilizing vancomycin onto the surface of a magnetic chitosan-graphene (VCM-MCG) composite. An antibacterial effect is achieved when VCM-MCG is applied. This effect is enhanced when the nanocomposites are irradiated with a near-infrared laser. Growth of gram-positive methicillin-resistant Staphylococcus aureus and gram-negative Escherichia coli bacteria are suppressed efficiently. Such a composite can help manage the control of pathogenic bacteria growth in the clinic.

High-Performance Intraocular Biosensors from Chitosan-Functionalized Nitrogen-Containing Graphene for the Detection of Glucose.

The noninvasive and real-time detection of glucose sugar from tears is promising for the early diagnosis and treatment of chronic diseases such as diabetes. However, its realization is a big challenge. A suitable biosensor electrode that can closely fit the eye and be electrochemically sensitive is still unrealized. In this work, nitrogen-doped graphene (N-G) was used as an ophthalmic electrode in a high-performance intraocular biosensor. The use of N-G has been reported elsewhere before as it is highly electroactive and so has a particular use in biosensors. We hereby present a novel procedure for making carboxylated chitosan-functionalized nitrogen-containing graphene (GC-COOH) by using a one-step ball-milling process. This process does not use toxic chemicals, flammable gases, or a high temperature. It is thus particularly easy to perform. The fabricated nanomaterial had a high electroactivity and was easily assembled as a glucose biosensor by the immobilization of glucose oxidase. The thus constructed biosensor has a high sensitivity at 9.7 µA mM-1 cm-2, a broad linear range at 12 mM, and a good detection limit of 9.5 µM. It was able to maintain this activity after a month of storage. We also report the intraocular use of this constructed biosensor. The as-prepared GC-COOH was found to be highly biocompatible to ophthalmologic cells such as corneal epithelial and retinal pigment epithelium cells. No change in the intraocular pressure or the corneal structure was measured in a New Zealand white rabbit model. The as-assembled sensor was worn by the animals for more than 24 h without undue impact. This result confirmed the biosensor's potential for intraocular application in the clinic. Its assembly into a useful sensor shown here has great potential to provide real-time monitoring of glucose levels in tear fluids of patients with high sugar levels.

Hydroxyl-Functional Groups on Graphene Trigger the Targeted Delivery of Antitumor Drugs.

An efficient and targeted treatment for tumor cells is demonstrated. This targeting is based upon the strong affinity between hydroxyl-functional groups on graphene and acidic tumors. The hydroxylated graphene (GOH) with a unique 2D architecture further improve the targeting capacity of the system via an enhanced permeability and retention (EPR) process. Polyethylene glycol (PEG) was employed for better biocompatibility and the antitumor drug doxorubicin (DOX) was then incorporated. These additions created a biocompatible system with a superior pH-dependent drug release property. Its proficiency was due to its ability to pass through cell membranes via a process of endocytosis and exocytosis. The results from a Transwell co-culture system discovered that the PEG-GOH-DOX system had a large impact on tumor cell viability (less than 10% survived after treatment) and little influence on normal cells (more than 80% survived). An in vitro 3D tumor model study demonstrated that the size of the PEG-GOH-DOX treated tumor was 50% less than that of the pristine DOX treated tumor. In vivo data indicated that the PEG-GOH-DOX system was able to inhibit the size of tumors by a factor of 6.5 when compared to the untreated tumors.

A Transferrin Triggered Pathway for Highly Targeted Delivery of Graphene-Based Nanodrugs to Treat Choroidal Melanoma.

The synthesis of transferrin (Tf)-modified pegylated graphene (PG) and its application as a highly efficient drug delivery carrier for therapy of Ocular Choroidal Melanoma-1 (OCM-1) cells is presented. For the first reported time, nanoscaled PG is prepared using an environmentally friendly ball-milling technique. The unique 2D nanostructure obtained using this PG synthesis approach offers considerable advantages in terms of drug loading and delivery, as well as the conjugation of Tf to PG providing a more targeted delivery vehicle. A highly efficient targeted pathway toward OCM-1 cells triggered by an affinity between Tf and Tf receptors expressed on the surface of OCM-1 cells is reported first here. PG-Tf is observed to easily anchor anticancer drugs such as doxorubicin via π-π stacking. This work performs a Transwell two cells coculture experiment, a 3D in vitro tumor model, and an in vivo mouse model with OCM-1 tumors to demonstrate the composite's therapeutic superiority over conventional systems for the targeted delivery and controlled release of antitumor drugs.