7 research outputs found
Graphene Oxide Based Theranostic Platform for <i>T</i><sub>1</sub>‑Weighted Magnetic Resonance Imaging and Drug Delivery
Magnetic
resonance imaging (MRI) is a powerful and widely used clinical technique
in cancer diagnosis. MRI contrast agents (CAs) are often used to improve
the quality of MRI-based diagnosis. In this work, we developed a positive <i>T</i><sub>1</sub> MRI CA based on graphene oxide (GO)–gadolinium
(Gd) complexes. In our strategy, diethylenetriaminepentaacetic acid
(DTPA) is chemically conjugated to GO, followed by Gd(III) complexation,
to form a <i>T</i><sub>1</sub> MRI CA (GO–DTPA–Gd).
We have demonstrated that the GO–DTPA–Gd system significantly
improves MRI <i>T</i><sub>1</sub> relaxivity and leads to
a better cellular MRI contrast effect than Magnevist, a commercially
used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on
the surface of GO sheets via physisorption. Thus-prepared GO–DTPA–Gd/DOX
shows significant cytotoxicity to the cancer cells (HepG2). This work
provides a novel strategy to build a GO-based theranostic nanoplatform
with <i>T</i><sub>1</sub>-weighted MRI, fluorescence imaging,
and drug delivery functionalities
PEGylated Graphene Oxide-Mediated Protein Delivery for Cell Function Regulation
Delivery of proteins into cells may alter cellular functions
as
various proteins are involved in cellular signaling by activating
or deactivating the corresponding pathways and, therefore, can be
used in cancer therapy. In this study, we have demonstrated for the
first time that PEGylated graphene oxide (GO) can be exploited as
a nanovector for efficient delivery of proteins into cells. In this
approach, GO was functionalized with amine-terminated 6-armed polyethylene
glycol (PEG) molecules, thereby providing GO with proper physiological
stability and biocompatibility. Proteins were then loaded onto PEG-grafted
GO (GO-PEG) with high payload via noncovalent interactions. GO-PEG
could deliver proteins to cytoplasm efficiently, protecting them from
enzymatic hydrolysis. The protein delivered by GO-PEG reserves its
biological activity that regulates the cell fate. As a result, delivery
of ribonuclease A (RNase A) led to cell death and transport of protein
kinase A (PKA) induced cell growth. Taken together, this work demonstrated
the feasibility of PEGlyated GO as a promising protein delivery vector
with high biocompatibility, high payload capacity and, more importantly,
capabilities of protecting proteins from enzymatic hydrolysis and
retaining their biological functions
Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating
The advent and pending wide use of nanoscale materials urges a biosafety assessment and safe design of nanomaterials that demonstrate applicability to human medicine. In biological microenvironment, biomolecules will bind onto nanoparticles forming corona and endow nanoparticles new biological identity. Since blood-circulatory system will most likely be the first interaction organ exposed to these nanomaterials, a deep understanding of the basic interaction mechanisms between serum proteins and foreign nanoparticles may help to better clarify the potential risks of nanomaterials and provide guidance on safe design of nanomaterials. In this study, the adsorption of four high-abundance blood proteins onto the carbon-based nanomaterial graphene oxide (GO) and reduced GO (rGO) were investigated <i>via</i> experimental (AFM, florescence spectroscopy, SPR) and simulation-based (molecular dynamics) approaches. Among the proteins in question, we observe competitive binding to the GO surface that features a mélange of distinct packing modes. Our MD simulations reveal that the protein adsorption is mainly enthalpically driven through strong π–π stacking interactions between GO and aromatic protein residues, in addition to hydrophobic interactions. Overall, these results were in line with previous findings related to adsorption of serum proteins onto single-walled carbon nanotubes (SWCNTs), but GO exhibits a dramatic enhancement of adsorption capacity compared to this one-dimensional carbon form. Encouragingly, protein-coated GO resulted in a markedly less cytotoxicity than pristine and protein-coated SWCNTs, suggesting a useful role for this planar nanomaterial in biomedical applications
Light-Enhanced Antibacterial Activity of Graphene Oxide, Mainly via Accelerated Electron Transfer
Before graphene derivatives can be
exploited as next-generation
antimicrobials, we must understand their behavior under environmental
conditions. Here, we demonstrate how exposure to simulated sunlight
significantly enhances the antibacterial activity of graphene oxide
(GO) and reveal the underlying mechanism. Our measurements of reactive
oxygen species (ROS) showed that only singlet oxygen (<sup>1</sup>O<sub>2</sub>) is generated by GO exposed to simulated sunlight,
which contributes only slightly to the oxidation of antioxidant biomolecules.
Unexpectedly, we find the main cause of oxidation is light-induced
electron–hole pairs generated on the surface of GO. These light-induced
electrons promote the reduction of GO, introducing additional carbon-centered
free radicals that may also enhance the antibacterial activities of
GO. We conclude that GO-mediated oxidative stress mainly is ROS-independent;
simulated sunlight accelerates the transfer of electrons from antioxidant
biomolecules to GO, thereby destroying bacterial antioxidant systems
and causing the reduction of GO. Our insights will help support the
development of graphene for antibacterial applications
Facet Energy <i>versus</i> Enzyme-like Activities: The Unexpected Protection of Palladium Nanocrystals against Oxidative Damage
To
develop nanomaterials as artificial enzymes, it is necessary
to better understand how their physicochemical properties affect their
enzyme-like activities. Although prior research has demonstrated that
nanomaterials exhibit tunable enzyme-like activities depending on
their size, structure, and composition, few studies have examined
the effect of surface facets, which determine surface energy or surface
reactivity. Here, we use electron spin-resonance spectroscopy to report
that lower surface energy {111}-faceted Pd octahedrons have greater
intrinsic antioxidant enzyme-like activity than higher surface energy
{100}-faceted Pd nanocubes. Our <i>in vitro</i> experiments
found that those same Pd octahedrons are more effective than Pd nanocubes
at scavenging reactive oxygen species (ROS). Those reductions in ROS
preserve the homogeneity of mitochondrial membrane potential and attenuate
damage to important biomolecules, thereby allowing a substantially
higher number of cells to survive oxidative challenges. Our computations
of molecular mechanisms for the antioxidant activities of {111}- and
{100}-faceted Pd nanocrystals, as well as their activity order, agree
well with experimental observations. These findings can guide the
design of antioxidant-mimicking nanomaterials, which could have therapeutic
or preventative potential against oxidative stress related diseases
Crossover between Anti- and Pro-oxidant Activities of Graphene Quantum Dots in the Absence or Presence of Light
Graphene
quantum dots (GQDs), zero-dimensional carbon materials
displaying excellent luminescence properties, show great promise for
medical applications such as imaging, drug delivery, biosensors, and
novel therapeutics. A deeper understanding of how the properties of
GQDs interact with biological systems is essential for these applications.
Our work demonstrates that GQDs can efficiently scavenge a number
of free radicals and thereby protect cells against oxidative damage.
However, upon exposure to blue light, GQDs exhibit significant phototoxicity
through increasing intracellular reactive oxygen species (ROS) levels
and reducing cell viability, attributable to the generation of free
radicals under light excitation. We confirm that light-induced formation
of ROS originates from the electron–hole pair and, more importantly,
reveal that singlet oxygen is generated by photoexcited GQDs <i>via</i> both energy-transfer and electron-transfer pathways.
Moreover, upon light excitation, GQDs accelerate the oxidation of
non-enzymic anti-oxidants and promote lipid peroxidation, contributing
to the phototoxicity of GQDs. Our results reveal that GQDs can display
both anti- and pro-oxidant activities, depending upon light exposure,
which will be useful in guiding the safe application and development
of potential anticancer/antibacterial applications for GQDs
Bactericidal Effects of Silver Nanoparticles on Lactobacilli and the Underlying Mechanism
While
the antibacterial properties of silver nanoparticles (AgNPs)
have been demonstrated across a spectrum of bacterial pathogens, the
effects of AgNPs on the beneficial bacteria are less clear. To address
this issue, we compared the antibacterial activity of AgNPs against
two beneficial lactobacilli (<i>Lactobacillus delbrueckii subsp.
bulgaricus</i> and <i>Lactobacillus casei</i>) and
two common opportunistic pathogens (<i>Escherichia coli</i> and <i>Staphylococcus aureus</i>). Our results demonstrate
that those lactobacilli are highly susceptible to AgNPs, while the
opportunistic pathogens are not. Acidic environment caused by the
lactobacilli is associated with the bactericidal effects of AgNPs.
Our mechanistic study suggests that the acidic growth environment
of lactobacilli promotes AgNP dissolution and hydroxyl radical (•OH)
overproduction. Furthermore, increases in silver ions (Ag<sup>+</sup>) and •OH deplete the glutathione pool inside the cell, which
is associated with the increase in cellular reactive oxygen species
(ROS). High levels of ROS may further induce DNA damage and lead to
cell death. When <i>E. coli</i> and <i>S. aureus</i> are placed in a similar acidic environment, they also become more
susceptible to AgNPs. This study provides a mechanistic description
of a pH-Ag<sup>+</sup>-•OH bactericidal pathway and will contribute
to the responsible development of products containing AgNPs