Methods to Scale Down Graphene Oxide Size and Size Implication in Anti-cancer Applications

Abstract

Despite considerable progress in the comprehension of the mechanisms involved in the origin and development of cancer, with improved diagnosis and treatment, this disease remains a major public health challenge with a considerable impact on the social and economic system, as well as on the individual. One way to improve effectiveness and reduce side effects is to consider responsive stimuli delivery systems that provide tailor-made release profiles with excellent spatial and temporal control. 2D nanomaterials possess special physicochemical properties (e.g., light, ultrasonic and magnetic responses) and biological behaviors such as endocytosis, biodistribution, biodegradation, and excretory pathways, which lead to their use in various biomedical applications. In particular, among 2D nanomaterials, graphene and its derivatives, namely graphene oxide (GO) nanomaterials, have attracted enormous attention in cancer diagnosis and therapy because they combine, in a unique material, extremely small size, NIR absorption, delocalized electrons, extremely high surface area, and versatile surface functionality. Taking into account the fundamental role played by GO size, in this review, we summarize the main methods employed to reduce and homogenize in nanometric scale the lateral dimensions of graphene oxide produced by chemical exfoliation of graphite, as well as post-synthesis separation techniques to uniform the size. We also discuss the implication of the small size in cancer treatment by exploiting GO nanocarriers as an effective theranostic tool.

High-Yield Production of Nano-Lateral Size Graphene Oxide by High-Power Ultrasonication

“…It is important to notice that, in our method, we produce GOn directly from GtO, contrary to the previously mentioned work, where previously exfoliated GO (not GtO) is size reduced. Analysis of C1s spectra of both GO and GOn revealed two large peaks, which could be further deconvoluted in five peaks centered at 284.5, 286.7, 287.9, 288.5, and 292.6 eV (Figure 8A, Table 2), which can be attributed to the formation of: (1) sp 2 and sp 3 hybridizations of carbon (C-C and C=C, C1s at % = 45.5 for GO and C1s at % = 38.4 for GOn) in the graphitic backbone; (2) single bonds between carbon and oxygen (C-O) in hydroxyls and ethers (C1s at % = 44.9 for GO and C1s at % = 53.2 for GOn); (3) double bonds between carbon and oxygen (C=O), indicating the presence of carbonyl groups (C1s at % = 4.2% for GO and C1s at % = 2.8% for GOn); ( 4) multiple bonds between carbon and oxygen (O=C−O), indicating the occurrence of carboxyls (C1s at % = 4.5 for GO and C1s at % = 3.9 for GOn); and (5) π -π * bonds due to the presence of delocalized π electrons in the graphene lattice (C1s at % = 0.93 for GO and C1s at % = 1.8 for GOn) [3,12,23].…”

“…Graphene oxide (GO) with very small lateral dimensions, in the order of 100 nm or less -commonly designated as nanographene (GOn) -has been receiving increasing attention in the field of biomedicine, particularly in the area of cancer treatment. Proposed applications include uses as drug carriers, platforms for photothermal and photodynamic therapies or agents for biological imaging [1][2][3]. These take advantage of GOn's physico-chemical properties in combination with good biocompatibility and low toxicity.…”

“…avoiding reduction), has been the subject of several studies. These were recently reviewed by Tufano et al [2] and the main approaches involved can be summarized as:…”

High-Yield Production of Nano-Lateral Size Graphene Oxide by High-Power Ultrasonication

“…Graphene oxide (GO) with very small lateral dimensions, in the order of 100 nm or less-commonly designated as nanographene (GOn)-has been attracting increasing attention in the biomedical field, particularly in the area of cancer treatment. Proposed applications include uses as drug carriers, platforms for photothermal and photodynamic therapies, or agents for biological imaging [1][2][3]. These take advantage of GOn's physicochemical properties in combination with good biocompatibility and low toxicity.…”

“…The size of the GO platelets is a relevant parameter when considering biological systems, since it may affect absorption into the body, penetration into blood vessels, cellular uptake, renal clearance, and selective toxicity [2,8,9]. GO is most widely produced using the modified Hummers method, a graphite chemical oxidation/exfoliation process, yielding sheets with lateral dimensions of tens or hundreds of microns.…”