Abstract
Carbon nanomaterials have attracted increasing attention in biomedicine recently to be used as drug nanocarriers suitable for medical treatments, due to their large surface area, high cellular internalization and preferential tumor accumulation, that enable these nanomaterials to transport chemotherapeutic agents preferentially to tumor sites, thereby reducing drug toxic side effects. However, there are widespread concerns on the inherent cytotoxicity of carbon nanomaterials, which remains controversial to this day, with studies demonstrating conflicting results. We investigated here in vitro toxicity of various carbon nanomaterials in human epithelial colorectal adenocarcinoma (Caco-2) cells and human breast adenocarcinoma (MCF-7) cells. Carbon nanohorns (CNH), carbon nanotubes (CNT), carbon nanoplatelets (CNP), graphene oxide (GO), reduced graphene oxide (GO) and nanodiamonds (ND) were systematically compared, using Pluronic F-127 dispersant. Cell viability after carbon nanomaterial treatment followed the order CNP < CNH < RGO < CNT < GO < ND, being the effect more pronounced on the more rapidly dividing Caco-2 cells. CNP produced remarkably high reactive oxygen species (ROS) levels. Furthermore, the potential of these materials as nanocarriers in the field of drug delivery of doxorubicin and camptothecin anticancer drugs was also compared. In all cases the carbon nanomaterial/drug complexes resulted in improved anticancer activity compared to that of the free drug, being the efficiency largely dependent of the carbon nanomaterial hydrophobicity and surface chemistry. These fundamental studies are of paramount importance as screening and risk-to-benefit assessment towards the development of smart carbon nanomaterial-based nanocarriers.
Highlights
Carbon nanomaterials are promising new materials to be used as drug nanocarriers suitable for medical treatments in biomedicine, due to their large surface area and chemical stability that allows efficient loading of drugs via both covalent and non-covalent interactions [1,2,3]
The sequence in cell viability that resulted from the MTT assays for the different carbon nanomaterials tested here can be explained taking into account the surface chemistry of carbon nanomaterials
The highest viability values correspond to ND, whose surface is rich in functional groups, which make them ideal nanocarriers for building drug delivery systems
Summary
Carbon nanomaterials are promising new materials to be used as drug nanocarriers suitable for medical treatments in biomedicine, due to their large surface area and chemical stability that allows efficient loading of drugs via both covalent and non-covalent interactions [1,2,3] Their interaction with lipid membranes and their subsequent intracellular transport is poorly understood, it has been demonstrated that they can enter cells using various endocytic processes [4,5]. Representative examples, with different size, shape and functional groups on the surface, such as carbon nanohorns (CNH), carbon nanotubes (CNT), graphene nanoplatelets (CNP), graphene oxide (GO), reduced graphene oxide (RGO) and carbon nanodiamonds (ND) were systematically compared under the same experimental conditions Their potential in the field of drug delivery of anticancer drugs, such as doxorubicin (DOX) and camptothecin (CPT), was compared in this work. It has to be noted that the cancer cell lines targeted here, Caco-2 and MCF-7, correspond to cancers among those having the highest incidence in Western countries, the interest of anticancer therapeutic studies performed on them
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