Folic Acid-Functionalized Albumin/Graphene Oxide Nanocomposite to Simultaneously Deliver Curcumin and 5-Fluorouracil into Human Colorectal Cancer Cells: An In Vitro Study (original) (raw)

Folic-Acid-Functionalized Graphene Oxide Nanocarrier: Synthetic Approaches, Characterization, Drug Delivery Study, and Antitumor Screening

ACS Applied Nano Materials, 2018

In this work, we developed and screened the potential anti-tumor activity of a nanocarrier based on graphene oxide (GO) and folic acid (FA) for the delivery of chemotherapy drugs. GO was synthesized by the graphite exfoliation process. FA was linked to PEG (4,7,10-trioxa-1,13-tridecanediamine) to form FA-PEG, followed by coupling to the GO surface. Camptothecin (CPT) was further adsorbed on GO for use as a drug model in the delivery study. The synthesis of the intermediate FA-PEG molecule and coupling to GO for the formation of the GO-FA nanocarrier was confirmed by basic and state-of-the-art characterization techniques, including infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), electrospray ionization (ESI) mass spectrometry, transmission electron microscopy (TEM), and magic-angle spinning carbon-13 nuclear magnetic resonance (CP/MAS 13 C NMR) spectroscopy. FTIR spectroscopy showed a significant reduction in the signal intensity of the carboxylic groups after the

Preparation and anti-cancer activity of transferrin/folic acid double-targeted graphene oxide drug delivery system

Journal of Biomaterials Applications, 2020

In this study, a transferrin/folic acid double-targeting graphene oxide drug delivery system loaded with doxorubicin was designed. Graphene oxide was prepared by ultrasound improved Hummers method and was modified with Pluronic F68, folic acid, and transferrin to decrease its toxicity and to allow dual-targeting. The results show that the double target drug delivery system (TFGP*DOX) has good and controllable drug delivery performance with no toxicity. Moreover, TFGP*DOX has a better inhibitory effect on SMMC-7721 cells than does a single target drug delivery system (FGP*DOX). The results of drug release analysis and cell inhibition studies showed that TFGP*DOX has a good sustained release function that can reduce the drug release rate in blood circulation over time and improve the local drug concentration in or near a targeted tumor. Therefore, the drug loading system (TFGP*DOX) has potential application value in the treatment of hepatocellular carcinoma.

Synthesis and stability analysis of folic acid-graphene oxide nanoparticles for drug delivery and targeted cancer therapies

International advanced researches and engineering journal, 2019

Cancer is the growth and proliferation of damage-ending cells in an uncontrolled or abnormal way. Today, it takes place among the most important health problems around the world and in our country. Surgery, radiotherapy, and chemotherapy are the main treatment methods in cancer treatment. The development of resistance to chemotherapeutic medicines has led scientists to investigate this issue as well as the drug's ability to reach the targeted tumor site and destroying cancer cells in addition to normal cells. The production of various nanostructures for anticancer drug development has been one of the most important areas of nanomedicine. Thus, in the present research, the improved Hummers' method was employed for the synthesis of graphene oxide nanoparticle (NGO), and it was activated by the folic acid (FA) antibody to increase targeting ability after attachment of the drug to the nanostructure systems. SEM, FTIR, XRD, UV/Vis spectroscopy, and zeta potential analysis were performed for characterization of the products. The highest absorbance of the FA-NGO/DIW nanostructures produced at the concentration of 0.01 mg/ml-0.05 mg/ml synthesized by the Hummers' method and in the UV/Vis spectra, peaks at 232 nm and 270 nm corresponds to NGO-DIW and FA-NGO/DIW, respectively. The zeta potential value above 35 mV was obtained in all measurements, and the NGO-DIW and NGO-FA-DIW samples maintained stability for days. These findings are consistent with the few studies in the literature, and this study will guide future studies in which nanoparticle systems will be directed to the target by binding chemotherapeutic drugs.

Camptothecin loaded graphene oxide nanoparticle functionalized with polyethylene glycol and folic acid for anticancer drug delivery

Journal of Drug Delivery Science and Technology, 2018

Graphene oxide nanomaterials are widely used to achieve effective cancer treatment. In this study, a novel graphene oxide mediated drug delivery system was synthesized by combining anticancer drug camptothecin (CPT) to the large surface area of graphene oxide by π-π stacking. Initially graphene oxide was synthesized by hummer's method and to obtain a more precise drug delivery, the system was loaded onto polyethylene glycol (PEG) decorated with folic acid. The resultant conjugate was characterized by Fourier Transform Infrared spectroscopy (FTIR), X-Ray Diffraction (XRD) analysis, UV-visible Spectrophotometery, Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The graphene-oxide-polyethylene glycol-folic acid-camptothecin (GO-PEG-FA-CPT) drug delivery system showed a pH dependent drug release as observed by UV analysis. The anticancer activity of the synthesized drug delivery system was studied by MTT assay using MCF-7 breast cancer cell lines. The conjugate showed enhanced anticancer activity and thus could be used as a potential candidate for drug delivery.

5-Fluorouracil and curcumin co-encapsulated chitosan/reduced graphene oxide nanocomposites against human colon cancer cell lines

Polymer Bulletin, 2019

Recent attention on chemotherapy against cancer is to explore the effective therapy through targeted delivery of anticancer agents to the tumor site by manipulating pharmacokinetic properties of nanocarriers. 5-Fluorouracil (5-FU) and curcumin (CUR) loaded chitosan/reduced graphene oxide (CS/rGO) nanocomposite has been prepared via simple chemical method. The polymer matrix-type chitosan/ rGO nanocomposite, before and after encapsulation, has been analyzed by various characterizations. Entrapment and loading efficiencies were estimated. The results that demonstrated higher entrapment efficiency (> 90%) were achieved by CS/rGO nanocarrier. Various kinetic models were used to analyze the release model and to elucidate the release mechanism of the drug from CS/rGO nanocomposite. The synergistic cytotoxicity was observed on addition of 5-FU + CUR-loaded CS/rGO nanocomposite which shows the effectiveness of the system toward the inhibition of growth of HT-29 colon cancer cells. The better cytotoxicity with an IC 50 of 23.8 μg/ mL was observed for dual-drug-loaded nanocomposite.

Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell

International Journal of Molecular Sciences, 2020

The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites’ ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the...

Highly Enhanced Loading Quality of Curcumin onto Carboxylated Folate Graphene Oxide

Scientia Iranica, 2018

This research focuses on loading of curcumin (Cur) anticancer drug onto nanocarriers, based on graphene oxide (GO), and improvement of loading efficiency. Surface of synthesized GO was modified by citric acid (CA) and functionalized by folic acid (FA) as a targeting agent. The functionalized GO by CA (CGO) and FA (GO-FA) were analyzed by Fourier transform infrared (FTIR). Furthermore FA was conjugated to the composite of CGO to prepare stabilized and targeted GO. The CGO-FA composite was characterized by FTIR and scanning electron microscopy (SEM) analysis. Thereafter, Cur as hydrophobic drug was loaded onto GO, CGO, GO-FA, and CGO-FA. Loaded Cur onto GO was characterized by SEM, FTIR and UV-Vis spectrophotometry. To increase the loading efficiency of Cur, the effects of water and ethanol as solvents and the weight ratios of initial Cur to GO (Cur/GO) were evaluated on the loading efficiency by response surface methodology. Comparing the loaded drug efficiencies onto different carri...

Folic Acid-decorated and PEGylated Graphene Quantum Dots as efficient Tamoxifen delivery system against breast cancer cells: in vitro studies

Nano-drug delivery systems have provided a platform for improving the formulations of targeted cancer therapy. Graphene quantum dots (GQDs) possess potential properties for the targeted transport and tracking of anticancer medication to tumor cells. For this purpose, the synthesized GQDs were decorated with folic acid for better binding to folate-positive breast cancer cells and methoxy polyethylene glycol (mPEG2000) for a longer lifetime, and finally loaded with anticancer drug tamoxifen (TMX). The synthesized nano-drugs were characterized using FTIR, XRD, UV-vis, PL, HRTEM, FESEM, and DLS analytical devices. Based on the obtained data, the average hydrodynamic diameter of particles dissolved in water was 294.7 nm and the size of dehydrated particles was between 3 and 153 nm. PL data showed that prepared nanoparticles have an emission wavelength of 438 nm, which is in the blue fluorescent wavelength range, thus making these nanoparticles suitable for cell imaging. The encapsulation...

Fabrication and characterization of a triple functionalization of graphene oxide with Fe3O4, folic acid and doxorubicin as dual-targeted drug nanocarrier

Colloids and Surfaces B: Biointerfaces, 2013

A novel triple functionalized drug delivery system was synthesized by encapsulation of superparamagnetic graphene oxide (GO) and doxorubicin (DOX) with folic acid (FA) conjugated chitosan (CHI). The carrier exhibited a high loading efficiency (0.98 mg/mg), a high saturation magnetization (10.5 emu/g) and a prolonged release rate. A real-time monitoring method on the drug release from graphene oxide (GO) was reported using DOX as the model drug. The release mechanism of DOX at different pH was investigated via monitoring the time dependency of the accumulative drug release. Results show that the drug release of DOX was pH sensitive as observed at pH 5.3 and pH 7.4 PBS solutions, the lower pH values lead to weaker hydrogen bonds and degradation of CHI, and thus result in a higher release rate of DOX. Especially, this system could be applied as a dual-targeted drug nanocarrier by combined biological (active) and magnetical (passive) targeting capabilities. Our research suggests that a novel triple functionalized, pH-responsive nanocarrier for anticancer drug has been synthesized.

Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma

Materials, 2021

Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites’ physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential...