Multiresponsive carboxylated graphene oxide-grafted aptamer as a multifunctional nanocarrier for targeted delivery of chemotherapeutics and bioactive compounds in cancer therapy

Fatemeh Yaghoubi,Seyed Morteza Naghib,Fateme Haghiralsadat,Najmeh Sadat Hosseini Motlagh,Davood Tofighi,Hossein Zarei Jaliani,Ali Moradi

doi:10.1515/ntrev-2021-0110

Abstract

AbstractTo date, the use of nanocarriers has been developed in various fields, especially in cancer treatment. Graphene oxide (GO) is a novel drug delivery system that eagerly attracts the attention of many researchers due to its unique features. For the first time, a biocompatible AS1411 APT-GO-COOH was synthesized for the co-delivery of chemotherapeutics and herbal drugs. Here, a human gastric adenocarcinoma cell line (AGS) was targeted with aptamer-carboxylated graphene oxide (APT-CGO) containing anticancer drugs (curcumin (CUR) and doxorubicin (DOX)). The current study aimed to assess the anti-cancer effect of combination therapy, as well as target genes and proteins interfering in the development of gastric cancer. After attachment of APT to CGO, the drugs (CUR and DOX) were loaded on the carrier, establishing a co-delivery system. Then, physical characteristics, release profile, cytotoxicity assay, cellular uptake, expression rates of the genes (RB1, CDK2, AKT, and NF-KB) and proteins (RB1, CDK2), and the apoptosis rate were determined. The designed co-delivery system for the drugs (CUR and DOX) and APT showed a thermo- and pH-sensitive drug release behavior that successfully reduced the expression of CDK2, AKT, and NF-KB while it enhanced RB1 expression at the gene and protein levels. Also, APT-CGO-drugs were successfully targeted to the AGS cell line, leading to a highly inhibitory property against this cell line compared to CGO-drugs. It seems that the co-delivery of CUR and DOX along with APT as a targeting agent was more effective than CGO-drugs, suggesting a promising candidate for the treatment of gastric cancer. The results showed that this biofunctionalized nanocarrier could reduce the cytotoxicity of the drugs in normal cells and could increase efficiency.

Highlights

Despite common strategies for the treatment of cancer, it remains a major cause of morbidity and mortality worldwide [1,2]
Surface charge expressed as zeta potential plays a key role in cellular interactions that is determined by dynamic light scattering (DLS)
The current study evaluated the expression of RB1, CDK2, AKT1, and NF-KB genes, which were involved in different pathways, regulating the survival of cancer cells

Summary

Introduction

Despite common strategies for the treatment of cancer (surgery, chemotherapy, and radiotherapy), it remains a major cause of morbidity and mortality worldwide [1,2]. The efficiency of chemotherapy has been proved in recent years, the serious obstacle is its side effects on normal cells and toxicity [3]. Extensive heterogeneity of tumor cells and drug resistance count as other. Multi-responsive aptamer-graphene oxide for cancer therapy 1839 obstacles in cancer treatment, which cause the efflux of anticancer agents from cancer cells [4]. Heterogeneity is derived from DNA instability and epigenetic differences of tumor cells, leading to diverse responses to therapy. Combination therapy can be applied as an effective strategy due to targeting several pathways of cancer cells [5]. Nanocarriers have attracted the attention of many researchers in the last few years [11,12,13], owing to their great advantages such as reducing the systemic toxicity of the loaded drugs, as well as their ability to deliver several drugs, simultaneously [14,15,16,17,18]

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