Particulate nanomedicines

On 29 December 1959 at the annual meeting of the American Physical Society at Caltech Richard Feynman delivered a lecture entitled “There's Plenty of Room at the Bottom” in which he stated “I leave to your imagination the improvement of the design to take full advantage of the properties of things on a small scale”. Feynman's statement has proven to be true, thanks to developments in nanotechnology, which are now having an impact on modern medicine. It is the intention of this Theme Issue of Advanced Drug Delivery Reviews (ADDR) to critically examine the potential biomedical application of promising nanoscale particulate materials, either in their own rights or as a component of multifunctional platforms, in the context of experimental disease detection and treatment following administration into the body. Indeed, the physical and chemical properties of a given material can significantly improve or radically change as size is down-scaled to small clusters of atoms (from a few to tens of nanometers) [1]. These include mechanical, thermal, electrical, magnetic, and light emission properties. This has led to development of an array of novel nanomaterials and nanocomposites the characteristics of which are beginning to have a paradigm-shifting impact in medicine; they are changing the foundations of disease diagnosis, monitoring and treatment, and turning promising molecular discoveries into benefits for patients (Table 1). For example, in semiconductor quantum dots (QDs), which are made of silicon and gallium arsenide core, there are discrete electronic energy levels (valance band and conduction band), but the spacing of the electronic energy levels (band gap) can be precisely controlled through variation in size [2]. When a photon, with higher energy than the energy of the band gap, hits a QD, an electron is promoted from valance band into the conduction band, leaving a hole behind. Electrons emit their excess energy as light when they recombine with holes. Since optical response is due to the excitation of single electron-hole pairs, the size and shape of QDs is easily tailored to fluoresce specific colours; a 2 nm QD (core size) luminesce bright green, while 5 nm QD luminesce red. The ability of QDs to tune broad wavelength together with their photostability is of paramount importance in biological labelling. As a result, we have seen developments for bio-conjugated QD for cell and macromolecular labelling, cell trafficking, and in vivo imaging [2] and [3]. For example, by reflectance imaging, one can follow lymphatic flow of intradermally injected water-soluble near infra-red type II QDs towards the sentinel lymph nodes and identify the position of lymph nodes up to 1 cm beneath the skin and 5 cm in lung tissue [3]. There are ongoing efforts to extend the wavelength at which QDs emit light above 900 nm (the current upper limit), since biomolecules rarely fluoresce above 1000 nm; this will make QD detectable at deeper levels in tissues. Other intriguing examples include QD conjugates that luminesce in cells and in animals by the naturally occurring bioluminescence resonance energy transfer (BRET) phenomenon in the absence of external excitation [4]. In BRET a light-emitting protein (e.g., Renilla reniformis luciferase) non-radiatively can transfer energy to an acceptor fluorescent protein in close proximity. Here, QDs simply replacing fluorescent proteins as BRET acceptor and therefore seem suitable for multiplexed imaging