ABSTRACT
Nanomedicine as a term first appeared in scientific articles in 2000 and employs nanoscale materials with unique medical effects [1]. A characteristic feature of nanotechnology based cancer medicines is that new functionality is added to existing products making them multifunctional, more potent via multivalency, and therefore
Keywords: C dots, ultrasmall fluorescent silica nanoparticles, fluorescent nanomaterials, fluorescence or dual-modality imaging, inorganic-organic hybrid nanoparticles, nanomedicine, molecular targeting, cancer imaging, first-in-human clinical trials, human metastatic melanoma, PET imaging, integrins, cyclo-Arg-Gly-Asp-Tyr (cRGDY)
more competitive [2, 3]. As an example, in cancer drug therapy liposomal formulations of existing drugs lower toxicity and increase targeting efficiency [4, 5]. Significant progress has been made in the past 15 years, and a number of nanomedicine products for cancer treatment are already on the market [6, 7]. But significant challenges lie ahead [8]. The chemistry of nanomaterials is not as well understood as that of molecules, and production of nanomedicines, e.g. based on dendrimers or pharmaceutical grade liposomes, is expensive [9]. Furthermore, while there is a tremendous pipeline of scientific projects on nanoscale materials for nanomedicine, only a vanishing small number actually gets into the clinic [10]. In order to safely translate laboratory innovation into the clinic, a workshop convened in 2008 by the FDA and the Alliance for Nano Health (ANH) identified seven priority areas to overcome top scientific hurdles for translation [11]. At the top of this list was the determination of biodistribution of nanoparticles as well as the development of imaging modalities for visualizing the biodistribution over time [11]. A more detailed discussion of these and other translational challenges that the field of nanomedicine faces, particularly as applied to cancer care settings, is provided elsewhere [12, 13]. Amongst the molecular imaging technologies perhaps the biggest growth area in oncology is occupied by optical/fluorescence imaging, and in particular by near infrared (NIR) fluorescence imaging [14, 15]. It is an inexpensive alternative to established imaging technologies (MRI, CT, PET), can be miniaturized (consider smart phones) for integration into minimally invasive surgical tools and promises to help visualize the expression and activity of particular molecules, cells and biological processes that influence the behavior of tumors and/or responsiveness to therapeutic drugs [16-18]. However, development and translation of NIRF nanoprobes have been slow as (i) fluorescent probes in water usually have low quantum yields, (ii) optical readouts are not quantitative, (iii) optical imaging is only relevant for tissue close to the skin surface, or tissue accessible by endoscopy and intraoperative visualization, (iv) there are considerable regulatory hurdles, and (v) there are lower profit margins for imaging than for therapeutic drugs [14, 15].
