General sites of nanoparticle biodistribution as a novel opportunity for nanomedicine.

The development of nanomedical devices has led to a considerable number of clinically applied nanotherapeutics. Yet, the overall poor translation of nanoparticular concepts into marketable systems has not met the initial expectations and led to increasing criticism in recent years. Most novel nano approaches thereby use highly refined formulations including a plethora of active targeting sequences, but ultimately fail to reach their target due to a generally high off-target deposition in organs such as the liver or kidney. In this context, we argue that initial nanoparticle (NP) development should not entirely become set on conventional formulation aspects. In contrast, we propose a change of focus towards a prior analysis of general sites of NP in vivo deposition and an assessment of how accumulation in these organs or tissues can be harnessed to develop therapies for site-related pathologies. We therefore give a comprehensive overview of existing nanotherapeutic targeting strategies for specific cell types within three of the usual suspects, i.e. the liver, kidney and the vascular system. We discuss the physiological surroundings and relevant pathologies of described tissues as well as the implications for NP-mediated drug delivery. Additionally, successful cell-selective NP concepts using active targeting strategies are assessed. By bringing together both (patho)physiological aspects and concepts for cell-selective NP formulations, we hope to show a novel opportunity for the development of more promising nanotherapeutic devices.