Nano Today
ReviewFunctionalisation of nanoparticles for biomedical applications
Introduction
Nanoparticles (NPs) are attracting considerable interest as viable biomedical materials and research into them is growing due to their unique physical and chemical properties. These NPs can be composed of a variety of materials including noble metals (e.g. Au [2], Ag [3], [4], Pt [5], Pd [6]), semiconductors (e.g. CdSe, CdS, ZnS [2], [7], TiO2 [8], PbS [9], InP [9], Si [10]), magnetic compounds (e.g. Fe3O4 [11], Co [12], CoFe2O4 [13], FePt [6], CoPt [14]) and their combinations (core–shell NPs and other composite nanostructures). Biomedical applications of NPs include drug carriers, labelling and tracking agents [2], [7], vectors for gene therapy, hyperthermia treatments and magnetic resonance imaging (MRI) contrast agents [5], [15]. In order for the NPs to be useful in biomedicine, they must satisfy certain criteria. For in vitro applications such as fluorescent staining of proteins and TEM imaging, NPs must outperform the conventional agents while having minimal cytotoxicity. In vivo, NPs have to avoid non-specific interactions with plasma proteins (opsonisation) and either evade or allow uptake by the reticuloendothelial system (RES) depending on the application, to reach their intended target efficiently. They must also maintain colloidal stability under physiological conditions, preferably including a wide range of pH. NPs carrying a payload, such as drug molecules or DNA for gene therapy must avoid premature release, yet specifically deliver the load to the desired site. Chemical modification of the NP surface is necessary for specific interactions with biomolecules of interest.
Section snippets
Synthesis in water
Nano-structured materials including Au [16], [17], Ag [4], Co [3], Nix [18] Fe3O4, Fe2O3, α-FeO(OH) [19], SiO2 [20] and CdTe [21], [22] have been synthesised in aqueous solution. These methods provide water-dispersible NPs, a necessity for the application in biological systems; however, control over particle size distribution is still limited for many semiconductor and magnetic NP systems. NP size affects the properties so a narrow size distribution is essential [23]. This can be reduced
Water solubilisation of nanoparticles
Water solubilisation may be carried out either as the final stage of the functionalisation process of NPs, or as an intermediate stage. It should be noted that the terms “solubilisation” and “solution” when applied to NPs does not refer to the solvation of the inorganic cores but rather the physically and chemically stable colloidal suspensions where NPs do not aggregate, dissociate, or chemically react to the solvent or any dissolved gas with time. Water solubilisation refers to the
Nucleic acids
The specific nature of DNA complementary binding is exploited in colorimetric assays for gene detection [159]. This strong, specific, non-covalent binding can also be employed to attach DNA-tagged NPs [60], [105], [160] to the surface of other NPs. However, it is worth noting that DNA is also capable of non-specific binding interactions with NPs, leading to less selective complementary binding interactions [161]. Non-specific binding of QDs to DNA has been shown to be entropically driven, this
Biomedical applications
The small nature of NPs allows them to cross cellular membranes and avoid detection by the reticuloendothelial system and their high surface area to volume ratio can allow increased loading of therapeutics; such properties makes NPs desirable for diagnostic and therapeutic applications which are briefly detailed, as follows [133], [203], [204].
NPs are employed for imaging in a variety of ways, both for medical purposes and further understanding of biochemical processes in vitro and in vivo [205]
Conclusion
In order to successfully prepare and biofunctionalise nanoparticles for a given biomedical application, a wide range of physical, chemical, biological and physiological factors and conditions must be taken into account. However, by tuning the nature of the core, shell and ligands, these factors can be taken advantage of to provide the desired, biocompatibility and biofunctionality, making inorganic nanocrystals suitable for a very wide range of applications in diagnostics and therapy for
Acknowledgements
Ian Robinson, Le Trong Lu, Daniel Dawson, Le Duc Tung and Cristina Blanco-Andujar are acknowledged for their helpful discussions and assistance. Nguyen T.K. Thanh thanks the Royal Society for her Royal Society University Research Fellowship. Luke Green is sponsored by a UCL-RI PhD studentship.
Dr Nguyen T.K. Thanh, FRSC, CChem, CSci, MRI, received the award for top academic achievement in Chemistry and was selected to study at the University of Amsterdam for her MSc in 1992. In 1994–1998, she read Biochemistry in London for PhD. In 1999, she undertook postdoctoral work in medicinal chemistry at Aston University, UK. In 2001, she moved to the United States to take advantage of pioneering work in nanotechnology. In 2003, she joined the Liverpool Centre for Nanoscale Science. In 2005,
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Dr Nguyen T.K. Thanh, FRSC, CChem, CSci, MRI, received the award for top academic achievement in Chemistry and was selected to study at the University of Amsterdam for her MSc in 1992. In 1994–1998, she read Biochemistry in London for PhD. In 1999, she undertook postdoctoral work in medicinal chemistry at Aston University, UK. In 2001, she moved to the United States to take advantage of pioneering work in nanotechnology. In 2003, she joined the Liverpool Centre for Nanoscale Science. In 2005, she was awarded a prestigious Royal Society University Research Fellowship and University of Liverpool Lectureship. In January 2009, she was appointed a UCL-RI Readership in Nanotechnology and based at the Davy Faraday Research Laboratory, The Royal Institution of Great Britain and Department of Physics and Astronomy, University College London. She leads a research team focused on the design, synthesis and study of the physical properties of nanomaterials as well as their applications in biomolecular and biomedical research.
Mr Luke A.W. Green, MChem, AMRSC, MRI, obtained his MChem with a year in Europe degree from the University of York in 2008. After a short spell working at a hospital biochemistry department, he is now studying for a PhD under the guidance of Dr Nguyen T.K. Thanh at UCL and is based at the Royal Institution of Great Britain. His interests are in the synthesis of magnetic nanoparticles for biomedical applications.