PEGylated nano-graphene oxide as a nanocarrier for delivering mixed anticancer drugs to improve anticancer activity

Xibo Pei,Zhoujie Gan,Xinting Cheng,Qianbing Wan,Junyu Chen,Xin Zhang,Zhou Zhu,Jian Wang

doi:10.1038/s41598-020-59624-w

Xibo Pei, Zhoujie Gan + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-59624-w

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Journal: Scientific Reports	Publication Date: Feb 17, 2020
Citations: 133	License type: open-access

Affiliation: Sichuan University

Abstract

Due to their high specific surface area, graphene oxide and graphene oxide-base nanoparticles have great potential both in dual-drug delivery and combination chemotherapy. Herein, we developed cisplatin (Pt) and doxorubicin (DOX) dual-drug-loaded PEGylated nano-graphene oxide (pGO) to facilitate combined chemotherapy in one system. In this study, nano-sized pGO-Pt/DOX ranged around 161.50 nm was fabricated and characterized using zeta-potential, AFM, TEM, Raman, UV-Vis, and FTIR analyses. The drug delivery efficacy of Pt was enhanced through the introduction of pGO, and the final weight ratio of DOX: Pt: pGO was optimized to 0.376: 0.376: 1. In vitro studies revealed that pGO-Pt/DOX nanoparticles could be effectively delivered into tumor cells, in which they induced prominent cell apoptosis and necrosis and exhibited higher growth inhibition than the single drug delivery system or free drugs. The pGO-Pt/DOX induced the most prominent cancer cell apoptosis and necrosis rate with 18.6%, which was observed almost 2 times higher than that of pGO-Pt or pGO-DOX groups. in the apoptosis and necrotic quadrants In vivo data confirmed that the pGO-Pt/DOX dual-drug delivery system attenuated the toxicity of Pt and DOX to normal organs compared to free drugs. The tumor inhibition data, histopathology observations, and immunohistochemical staining confirmed that the dual-drug delivery system presented a better anticancer effect than free drugs. These results clearly indicated that the pGO-Pt/DOX dual-drug delivery system provided the means for combination drug delivery in cancer treatment.

Highlights

Due to their high specific surface area, graphene oxide and graphene oxide-base nanoparticles have great potential both in dual-drug delivery and combination chemotherapy
Cisplatin was reacted with H2O2 and succinic anhydride to form Pt(NH3)2Cl2(OOCCH2CH2C-OOH) (OH) (abbreviated as Pt(IV) or Pt), and the Pt-loaded PEGylated nano-graphene oxide (pGO) nanoparticles was accomplished by a covalent reaction[19]
We developed a dual-drug delivery system using PEG-functionalized graphene oxide and antitumor drugs (Pt and DOX)

Summary

Introduction

Due to their high specific surface area, graphene oxide and graphene oxide-base nanoparticles have great potential both in dual-drug delivery and combination chemotherapy. The tumor inhibition data, histopathology observations, and immunohistochemical staining confirmed that the dual-drug delivery system presented a better anticancer effect than free drugs These results clearly indicated that the pGO-Pt/DOX dual-drug delivery system provided the means for combination drug delivery in cancer treatment. Some of the nanoparticles have been developed for the loading of doxorubicin and cisplatin, for example, Yunfeng[15] and Xueqiong[11] prepared dual-drug (doxorubicin and platinum-base compounds) delivery system using hollow mesoporous silica and carboxymethyl chitosan nanoparticles, respectively The results of both studies showed enhanced in vitro anticancer properties without in vivo study results, and the drug loading efficacy (DLE) of the dual drugs is relatively low. The advantage of this dual-drug delivery system was presented by detecting its drug delivery efficacy, drug releasing and cytotoxicity against cancer cells in vitro and in vivo

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