Photoresponsive Fluorescent Reduced Graphene Oxide by Spiropyran Conjugated Hyaluronic Acid for in Vivo Imaging and Target Delivery

Abstract

This present article demonstrates the strategy to prepare photoresponsive reduced graphene oxide with mussel inspired adhesive material dopamine (DN) and photochromic dye spiropyran (SP) conjugated to the backbone of the targeting ligand hyaluronic acid (HA; HA-SP). Graphene oxide (GO) was reduced by prepared HA-SP accepting the advantages of catechol chemistry under mildly alkaline condition enabling to achieve functionalized graphene (rGO/HA-SP) as fluorescent nanoparticles. Due to containing HA, rGO/HA-SP can bind to the CD44 cell receptors. The prepared rGO/HA-SP is able to retain its photochromic features and can be converted to merocyanine (MC) form upon irradiation with UV light (wavelength: 365 nm) displaying purple color. Photochromic behavior of rGO/HA-SP was monitored by UV-vis and fluorescence spectroscopy. In vitro fluorescence behavior, examined by confocal laser scanning microscope (CLSM), of rGO/HA-SP in cancerous A549 cell lines assured that efficient delivery of rGO/HA-SP was gained due to HA as targeting ligand. In this work, we have shown that in vivo fluorescence image of spiropyran is possible by administrating MC form solution of rGO/HA-SP using Balb/C mice as in vivo modal. Accumulation of rGO/HA-SP in tumor tissue from biodistribution analysis strongly supports the specific delivery of prepared graphene to the target destination. The well tuned drug release manner from the surface of rGO/HA-SP strongly recommends the developed material not only as fluorescent probe for diagnosis but also as a drug carrier in drug delivery system.

Direct noncovalent conjugation of folic acid on reduced graphene oxide as anticancer drug carrier

“…After removing unbound DOX from the solution of DOXloaded rGO/FA conjugate by ultracentrifuge, the DOX loading efficiently of 67.5% was observed when the concentrations of rGO/FA conjugate and the loaded DOX are 0.05 mg/mL and 20 μg/mL, respectively. This drug loading efficiency (or capacity) of rGO/FA conjugate is much higher than those of liposome-based common drug carrier materials (less than 10%) and comparable to that of recently reported drug carrier based on polymer-grafted rGO (76.25%) [42]. AFM image of DOX-loaded rGO/FA conjugate showed slightly increased plate thickness around 4.3 nm (Fig.…”

“…DOX shows the lowest cell viability (26.0%) at an equivalent dose because free DOX is able to enter into the cell through diffusion by spending a short time. Release of DOX from DOX-loaded rGO needs a comparatively long time due to the inevitable endocytosis of DOX-loaded rGO/FA conjugate [42].…”

Is Graphene a Promising Nano-Material for Promoting Surface Modification of Implants or Scaffold Materials in Bone Tissue Engineering?

“…It should be mentioned that most of the available data with regard to the toxicity and biocompatbility of graphene and its derivatives were obtained from studies on its potential use as a vehicle in drug delivery. 57,58,67,71,73 In this case, graphene and its derivatives are normally systemically administered, 67,71 or directly administered to organs of animals. 68,70 Thus, their biological reactions may be more obvious and direct.…”

Radio-graphene in Theranostic Perspectives

“…The same group also labeled a radioisotope ( 64 Cu) that has longer physical half-life (12.7 h) and TRC105 antibody onto GO before successfully determining the biodistribution, pharmacokinetics, and tumor targeting efficacy of this compound [27]. Another cancer-targeting approach using graphene was reported by Nahain, who designed a functionalized graphene by conjugating GO with photochromic dye spiropyran and hyaluronic acid (HA) [30]. The spiropyran, fluorescent material, enables finding the location of the graphene in the cells by circumventing the use of toxic effects of other dyes whilst the HA targets the cancer cells by easily binding to the CD44 receptor.…”

“…To overcome this toxic issue, the surface modifications can play a pivotal role in the improvement of biocompatibility by reducing the strong hydrophobic interaction of graphene or GO with cells and tissues as well as reducing the production of reactive oxygen species which is associated with apoptosis [35]. Polyethylene glycol (PEG) is an example of functionalized graphene that can facilitate the excretion of the nanoparticle without noticeable toxicity in vivo [30]. One of the most significant merits of using radiographene would be the ability to overcome the dosedependent toxicity issue by using a very small amount of radioactive materials for in vivo radionuclide imaging.…”