Graphene Oxide Loaded with Protocatechuic Acid and Chlorogenic Acid Dual Drug Nanodelivery System for Human Hepatocellular Carcinoma Therapeutic Application.

Kalaivani Buskaran,Mohamad Aris Mohd Moklas,Mas Jaffri Masarudin,Mohd Zobir Hussein,Sharida Fakurazi

doi:10.3390/ijms22115786

Kalaivani Buskaran, Mohamad Aris Mohd Moklas + Show 3 more

Open Access

https://doi.org/10.3390/ijms22115786

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Abstract

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75–90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide–polyethylene glycol (GOP)–PCA/CA–FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP–PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.

Highlights

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that accounts for 75–90% of all liver cancer in humans [1]
The polyethylene glycol (PEG) conjugated Graphene oxide (GO) will enhance the biocompatibility of the GO which enables the anticancer drug to bind to the graphene oxide surface through π–π stacking [25]
The combination of the dual drug loading is speculated to give a better result in terms of killing the cancer cells

Summary

Introduction

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that accounts for 75–90% of all liver cancer in humans [1]. Liver cancer has an assertive nature, which leads to poor survival rate and makes it a major public health problem in the world [2]. People from the Asia-Pacific region (East Asia and Southeast Asia) and Central and West African region are among those who are more prominently diagnosed with liver cancer [3]. The current treatments available for liver cancer are surgery, radiofrequency ablation, trans arterial chemoembolization and systemic chemotherapy [4]. There are side effects to these procedures where the systemic circulation of chemotherapy does not reside in the local accumulation of the diseased site but rather crosses cell barriers and damages the healthy cells as well [5]. The procedure that is used needs an expert in the field to conduct the procedures which causes an increase in the treatment cost [6]

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