Mark Green

Phospholipid Encapsulated Semiconducting Polymer Nanoparticles: Their Use in Cell Imaging and Protein Attachment

Semiconducting polymer nanospheres (SPNs) have been synthesized and encapsulated in phospholipid micelles by a solvent evaporation technique. Four different conjugated polymers were used, yielding aqueous dispersions of nanoparticles which emit across the visible spectrum. The synthesis was simple and easily reproducible, and the resultant nanoparticle solutions exhibited high colloidal stability. As these encapsulated SPNs do not contain any toxic materials and show favorable optical properties, they appear to be a promising imaging agent in biomedical and imaging applications. The SPNs were used in simple fluorescence imaging experiments and showed uptake in SH-SY5Y neuroblastoma and live HeLa cells. Carboxylic acid functionalized SPNs were also synthesized and conjugated to bovine serum albumin (BSA) by carbodiimide-mediated chemistry, a key step in the realization of targeted imaging using conjugated polymers.

The nature of quantum dot capping ligands

The synthesis of quantum dot semiconductors is now an established science and a large amount of work has been carried out into the chemistry and physics of the interface between nanoparticle surface and ligand. Here, we review the basic ligands and cover some of their properties.

Some aspects of quantum dot toxicity

Quantum dot toxicity has become a hot topic in recent years due to the emergence of semiconductor nanoparticles as highly efficient biological imaging agents. The use of quantum dots in biology is arguably the most successful application of pure nanotechnology in recent times, although unfortunately, the most useful semiconductor particles contain elements that are often thought to be detrimental to health and the environment. In this article, we explore some key reports on this issue.

Magnetic conjugated polymer nanoparticles as bimodal imaging agents.

Hybrid nanoparticles which incorporate multiple functionalities, such as fluorescence and magnetism, can exhibit enhanced efficiency and versatility by performing several tasks in parallel. In this study, magnetic-fluorescent semiconductor polymer nanospheres (MF-SPNs) have been synthesized by encapsulation of hydrophobic conjugated polymers and iron oxide nanoparticles in phospholipid micelles. Four fluorescent conjugated polymers were used, yielding aqueous dispersions of nanoparticles which emit across the visible spectrum. The MF-SPNs were shown to be magnetically responsive and simultaneously fluorescent. In MRI studies, they were seen to have a shortening effect on the transverse T(2)* relaxation time, which demonstrates their potential as an MR contrast agent. Finally, successful uptake of the MF-SPNs by SH-SY5Y neuroblastoma cells was demonstrated, and they were seen to behave as bright and stable fluorescent markers. There was no evidence of toxicity or adverse affect on cell growth.

Bisphosphonate-anchored PEGylation and radiolabeling of superparamagnetic iron oxide: long-circulating nanoparticles for in vivo multimodal (T1 MRI-SPECT) imaging

The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation times. To overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) group for strong and stable binding to the surface of ultrasmall-superparamagnetic oxide nanomaterials (USPIOs). This polymer, PEG(5)-BP, can be used to exchange the hydrophobic surfactants commonly used in the synthesis of USPIOs very efficiently and at room temperature using a simple method in 1 h. The resulting nanoparticles, PEG(5)-BP-USPIOs are stable in water or saline for at least 7 months and display a near-zero ζ-potential at neutral pH. The longitudinal (r1) and transverse (r2) relaxivities were measured at a clinically relevant magnetic field (3 T), revealing a high r1 of 9.5 mM–1 s–1 and low r2/r1 ratio of 2.97, making these USPIOs attractive as T1-weighted MRI contrast agents at high magnetic fields. The strong T1-effect was demonstrated in vivo, revealing that PEG(5)-BP-USPIOs remain in the bloodstream and enhance its signal 6-fold, allowing the visualization of blood vessels and vascular organs with high spatial definition. Furthermore, the optimal relaxivity properties allow us to inject a dose 4 times lower than with other USPIOs. PEG(5)-BP-USPIOs can also be labeled using a radiolabeled-BP for visualization with single photon emission computed tomography (SPECT), and thus affording dual-modality contrast. The SPECT studies confirmed low RES uptake and long blood circulation times (t1/2 = 2.97 h). These results demonstrate the potential of PEG(5)-BP-USPIOs for the development of targeted multimodal imaging agents for molecular imaging.

Biosynthesis of luminescent quantum dots in an earthworm

The synthesis of designer solid-state materials by living organisms is an emerging field in bio-nanotechnology. Key examples include the use of engineered viruses as templates for cobalt oxide (Co(3)O(4)) particles, superparamagnetic cobalt-platinum alloy nanowires and gold-cobalt oxide nanowires for photovoltaic and battery-related applications. Here, we show that the earthworms metal detoxification pathway can be exploited to produce luminescent, water-soluble semiconductor cadmium telluride (CdTe) quantum dots that emit in the green region of the visible spectrum when excited in the ultraviolet region. Standard wild-type Lumbricus rubellus earthworms were exposed to soil spiked with CdCl(2) and Na(2)TeO(3) salts for 11 days. Luminescent quantum dots were isolated from chloragogenous tissues surrounding the gut of the worm, and were successfully used in live-cell imaging. The addition of polyethylene glycol on the surface of the quantum dots allowed for non-targeted, fluid-phase uptake by macrophage cells.

A facile route to CdTe nanoparticles and their use in bio-labelling

A simple synthetic route to highly luminescent, water-soluble CdTe nanoparticles and their use in biological imaging is presented. The new synthetic pathway utilises a simply-prepared, water-soluble tellurium precursor which is easily handled and stored and the resulting growth processes are discussed.

Luminescent quantum-dot-sized conjugated polymer nanoparticles—nanoparticle formation in a miniemulsion system

The synthesis of semiconducting polymer nanospheres (SPNs) by miniemulsion methods has been reported previously,1,2 however the resulting materials have typically been significantly larger than quantum dots, the nanomaterial of choice for cell imaging. In the current work, we aimed to obtain quantum-dot-sized poly(ethylene-glycol) (PEG) functionalised SPNs by optimising the miniemulsion method reported previously.1,3 We report that PEG functionalised SPNs with a narrow distribution of quantum dot sizes were successfully synthesised, with mean diameters ranging between 2 and 5 nm. PEG-dithiol was also used in one variant of the syntheses, allowing the purified sample to be examined by mass spectrometry (using sulfur as a reporter), confirming the inclusion of a significant number of PEG molecules in the nanoparticles. Also, the presence of PEG was found to significantly affect the yield of the reaction, suggesting it played a role in nanoparticle formation. The nanoparticles were characterized by TEM, absorption and emission spectroscopy, and were found to be stable in solution for months.

Stem cell tracking using iron oxide nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.

Aluminium hydroxide stabilised MnFe2O4 and Fe3O4 nanoparticles as dual-modality contrasts agent for MRI and PET imaging

Magnetic nanoparticles (NPs) MnFe2O4 and Fe3O4 were stabilised by depositing an Al(OH)3 layer via a hydrolysis process. The particles displayed excellent colloidal stability in water and a high affinity to [18F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for 18F-fluoride and 100% for 64Cu-bisphosphonate conjugate, was achieved by simply incubating NPs with radioactivity solution at room temperature for 5 min. The properties of particles were strongly dependant on the thickness and hardness of the Al(OH)3 layer which could in turn be controlled by the hydrolysis method. The application of these Al(OH)3 coated magnetic NPs in molecular imaging has been further explored. The results demonstrated that these NPs are potential candidates as dual modal probes for MR and PET. In vivo PET imaging showed a slow release of 18F from NPs, but no sign of efflux of 64Cu.