In vivo single molecular imaging and sentinel node navigation by nanotechnology for molecular targeting drug-delivery systems and tailor-made medicine

Abstract

The recent advances in nanotechnology have a great potential to improve the prevention, diagnosis, and treatment of human diseases. Nanomaterials for medical applications are expected to grasp pharmacokinetics and the toxicity for application to medical treatment on the aspect of safety of the nanomaterials and nanodevices. We describe a generation of CdSe nanoparticles [quantum dots (QDs)] conjugated with monoclonal anti-HER2 antibody (Trastuzumab), for single molecular in vivo imaging of breast cancer cells. We established a high-resolution in vivo 3D microscopic system for a novel imaging method at the molecular level. The cancer cells expressing HER2 protein were visualized by the nanoparticles in vivo at subcellular resolution, suggesting future utilization of the system in medical applications to improve drug-delivery systems to target the primary and metastatic tumors for made-to-order treatment. We also describe sentinel node navigation using fluorescent nanoparticles for breast cancer surgery in experimental model, which have shown the potential to be an alternative to existing tracers in the detection of the sentinel node if we select the appropriate particle size and wavelength. Future innovation in cancer imaging by nanotechnology and novel measurement technology will provide great improvement, not only in the clinical field but also in basic medical science for the development of medicine.

Micro-CT enables microlocalisation and quantification of Her2-targeted gold nanoparticles within tumour regions

“…In other non-CT work, Herceptin has been used for targeted imaging using radioactivity [22], radioactive liposomes [18], magnetic nanoparticles [24], gadolinium [24][25][26] 18 F-PET [27], fluorophores [28][29][30] and near-infrared probes [28,31,32]. Consistent with these studies, we found a tumour uptake value (8.3% id g -1 ) similar to these other Herceptin adducts, indicating that the 15 nm AuNP-antibody conjugate delivery does not substantially alter the tumour uptake compared with, for example, a radiolabelled Herceptin antibody targeted to BT474 tumours, which showed 7.8% id g -1 localisation [22].…”

Advances in fluorescent-image guided surgery

“…These very small materials can be fine-tuned in order to fluoresce or to generate heat when excited in order to serve as fluorescent markers of cells and tissues or to target tissues for ablation. Groups have shown this technology to be useful even in in vivo single molecular imaging for sentinel node navigation; they specifically developed it for molecular targeting drug-delivery systems (136). These advances represent a paradigm shift in the way we think about operations and intraoperative imaging.…”

Nanoparticle delivery for metastatic breast cancer

“…Quantum dots have been the most extensively investigated nanoparticles for lymph node mapping [44][45][46][47][48]. Quantum dots have been demonstrated to accumulate in sentinel nodes following subcutaneous injection using fluorescence imaging (Fig.…”