In 2000, the National Institute of Health launched the National Nanotechnology Initiative to support, coordinate, and advance research and development of nanoscale projects. The impact of this new program on health-science related research and development became quickly visible. Broad governmental financial support advanced the start of new, and the deepening of already existing, interdisciplinary research. The anticipated merger of nanoscience with medicine quickly instigated the conceptualization of nanomedicine. The adoption of nanoscience terminology by pharmaceutical scientists resulted in the advent of nanopharmaceuticals. The term “nano” became tantamount to “cutting-edge” and was quickly embraced by the pharmaceutical science community. Colloidal drug delivery systems reemerged as nanodrug delivery systems; colloidal gold became a suspension of nano gold particles. In this review, we first review nanoscience related definitions applied to pharmaceuticals, we then discuss all 43 currently approved drug formulations which are publicized as nanopharmaceuticals, and finally we analyze clinical aspects of selected drug formulations.

In part I of this review we assessed nanoscience-related definitions as applied to pharmaceuticals and we discussed all 43 currently approved drug formulations, which are widely publicized as nanopharmaceuticals or nanomedicines. In continuation, here we review the currently ongoing clinical trials within the broad field of nanomedicine. Confining the definition of nanopharmaceuticals to therapeutic formulations, in which the unique physicochemical properties expressed in the nanosize range, when man-made, play the pivotal therapeutic role, we found an apparently low number of trials, which reflects neither the massive investments made in the field of nanomedicine nor the general hype associated with the term “nano.” Moreover, after an extensive search for information through clinical trials, we found only two clinical trials with materials that show unique nano-based properties, ie, properties that are displayed neither on the atomic nor on the bulk material level.

Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including those that induce mitochondria permeability transition and apoptosis, metabolic inhibitors, and ROS regulators. To date, however, none has exhibited the standards for high selectivity and efficacy and low toxicity necessary to progress beyond phase III clinical trials and be used as a viable, single modality treatment option for human cancers. This review explores alternative treatment strategies that have been shown to enhance the efficacy and selectivity of mitochondria-targeted anticancer agents in vitro and in vivo, and may yet fulfill the clinical promise of exploiting the mitochondrion as a target for cancer chemotherapy.