Neus Lozano

Liposome–Gold Nanorod Hybrids for High-Resolution Visualization Deep in Tissues

The design of liposome-nanoparticle hybrids offers a rich toolbox for the fabrication of multifunctional modalities. A self-assembled liposome-gold nanorod hybrid vesicular system that consists of lipid-bilayer-associated gold nanorods designed to allow deep tissue detection, therapy, and monitoring in living animals using multispectral optoacoustic tomography has been fabricated and characterized in vitro and in vivo.

Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks.

Graphene offers promising advantages for biomedical applications. However, adoption of graphene technology in biomedicine also poses important challenges in terms of understanding cell responses, cellular uptake, or the intracellular fate of soluble graphene derivatives. In the biological microenvironment, graphene nanosheets might interact with exposed cellular and subcellular structures, resulting in unexpected regulation of sophisticated biological signaling. More broadly, biomedical devices based on the design of these 2D planar nanostructures for interventions in the central nervous system require an accurate understanding of their interactions with the neuronal milieu. Here, we describe the ability of graphene oxide nanosheets to down-regulate neuronal signaling without affecting cell viability.

Purity of Graphene Oxide determines its antibacterial activity

Nanomaterials based on two-dimensional (2D) atomic crystals are considered to be very promising for various life-science and medical applications, from drug delivery to tissue modification. One of the most suitable materials for these purposes is graphene oxide (GO), thanks to a well-developed methods of production and water solubility. At the same time, its biological effect is still debated. Here we demonstrate that highly purified and thoroughly washed GO neither inhibited nor stimulated the growth of E.coli, ATCC25922; E.coli NCIMB11943 and S.aureus ATCC25923 at concentrations of up to 1 mg ml−1. Moreover, transmission electron microscopy (TEM) of GO exposed bacteria did not reveal any differences between GO exposed and not exposed populations. In contrast, a suspension of insufficiently purified GO behaved as an antibacterial material due to the presence of soluble acidic impurities, that could be removed by extended purification or neutralisation by alkaline substrates. A standardised protocol is proposed for the generation of clean GO, so it becomes suitable for biological experiments. Our findings emphasise the importance of GO purification status when dealing with biological systems as the true effect of material can be masked by the impact of impurities.

siRNA liposome-gold nanorod vectors for multispectral optoacoustic tomography theranostics †

Therapeutic applications of gene silencing using siRNA have seen increasing interest over the past decade. The optimization of the delivery and biodistribution of siRNA using liposome-gold nanorod (AuNRs) nanoscale carriers can greatly benefit from adept imaging methods that can visualize the time-resolved delivery performance of such vectors. In this work, we describe the effect of AuNR length incorporated with liposomes and show their complexation with siRNA as a novel gene delivery vehicle. We demonstrate the application of multispectral optoacoustic tomography (MSOT) to longitudinally visualize the localisation of siRNA carrying liposome-AuNR hybrids within tumors. Combination of in vivo MSOT with ex vivo fluorescence cryo-slice imaging offers further insight into the siRNA transport and activity obtained.

Engineering thermosensitive liposome-nanoparticle hybrids loaded with doxorubicin for heat-triggered drug release

The engineering of responsive multifunctional delivery systems that combine therapeutic and diagnostic (theranostic) capabilities holds great promise and interest. We describe the design of thermosensitive liposome-nanoparticle (NP) hybrids that can modulate drug release in response to external heating stimulus. These hybrid systems were successfully engineered by the incorporation of gold, silver, and iron oxide NPs into the lipid bilayer of lysolipid-containing thermosensitive liposomes (LTSL). Structural characterization of LTSL-NP hybrids using cryo-EM and AFM revealed the incorporation of metallic NPs into the lipid membranes without compromising doxorubicin loading and retention capability. The presence of metallic NPs in the lipid bilayer reinforced bilayer retention and offered a nanoparticle concentration-dependent modulation of drug release in response to external heating. In conclusion, LTSL-NP hybrids represent a promising versatile platform based on LTSL liposomes that could further utilize the properties of the embedded NPs for multifunctional theranostic applications.

Liposome-Indocyanine Green Nanoprobes for Optical Labeling and Tracking of Human Mesenchymal Stem Cells Post-Transplantation In Vivo

Direct labeling of human mesenchymal stem cells (hMSC) prior to transplantation provides a means to track cells after administration and it is a powerful tool for the assessment of new cell-based therapies. Biocompatible nanoprobes consisting of liposome-indocyanine green hybrid vesicles (liposome-ICG) are used to safely label hMSC. Labeled hMSC recapitulating a 3D cellular environment is transplanted as spheroids subcutaneously and intracranially in athymic nude mice. Cells emit a strong NIR signal used for tracking post-transplantation with the IVIS imaging system up to 2 weeks (subcutaneous) and 1 week (intracranial). The transplanted stem cells are imaged in situ after engraftment deep in the brain up to 1 week in living animals using optical imaging techniques and without the need to genetically modify the cells. This method is proposed for efficient, nontoxic direct cell labeling for the preclinical assessment of cell-based therapies and the design of clinical trials, and potentially for localization of the cell engraftment after transplantation into patients.

Hypochlorite degrades 2D graphene oxide sheets faster than 1D oxidised carbon nanotubes and nanohorns

Carbon nanostructures are currently fuelling a revolution in science and technology in areas ranging from aerospace engineering to electronics. Oxidised carbon nanomaterials, such as graphene oxide, exhibit dramatically improved water dispersibility compared to their pristine equivalents, allowing their exploration in biology and medicine. Concomitant with these potential healthcare applications, the issue of degradability has been raised and has started to be investigated. The aim of the present study was to assess the potential of hypochlorite, a naturally occurring and industrially used ion, to degrade oxidised carbon nanomaterials within a week. Our main focus was to characterise the physical and chemical changes that occur during degradation of graphene oxide compared to two other oxidised carbon nanomaterials, namely carbon nanotubes and carbon nanohorns. The kinetics of degradation were closely monitored over a week using a battery of techniques including visual observation, UV–Vis spectroscopy, Raman spectroscopy, infra-red spectroscopy, transmission electron microscopy and atomic force microscopy. Graphene oxide was rapidly degraded into a dominantly amorphous structure lacking the characteristic Raman signature and microscopic morphology. Oxidised carbon nanotubes underwent degradation via a wall exfoliation mechanism, yet maintained a large fraction of the sp2 carbon backbone, while the degradation of oxidised carbon nanohorns was somewhat intermediate. The present study shows the timeline of physical and chemical alterations of oxidised carbon nanomaterials, demonstrating a faster degradation of 2D graphene oxide sheets compared to 1D oxidised carbon nanomaterials over 7 days in the presence of an oxidising species.Carbon nanomaterials: graphene oxide degrades rapidly when exposed to hypochloriteOxidised carbon nanomaterials degrade into amorphous structures upon exposure to hypochlorite, a naturally occurring anion in human body. A team led by Kostas Kostarelos at the University of Manchester investigated the physical and chemical modifications occurring during degradation of graphene oxide and oxidised carbon nanotubes and nanohorns exposed to sodium hypochlorite, commonly known as bleach. The degradation pathways were followed over a week with the aid of advanced characterisation tools such as transmission electron microscopy, atomic force microscopy, and optical spectroscopy. Graphene oxide underwent a gradual reduction in dimensions followed by agglomeration and disintegration of its structure. Owing to its peculiar physicochemical features, graphene oxide degraded faster than the other two oxidized carbon nanostructures. These findings may help unveiling the toxicological profile of carbon nanomaterials.