Cancer nanomedicine: progress, challenges and opportunities

Although first-generation cancer nanomedicines have been in clinical practice for more than 20 years, the total number of papers related to 'nanoparticle' on PubMed nearly doubled every 2 years between 2000 and 2014, and more than half of the papers on nanoparticles have been published in the past 5 years, indicating that our knowledge and arsenal of cancer nanomedicines is rapidly expanding.Cancer nanomedicines accumulate in solid tumours through the enhanced permeability and retention (EPR) effect, which is increasingly appreciated to be complex, dynamic and heterogeneous across tumours and even within the same tumour.Identifying biomarkers for the EPR effect may enable selection of cancer patients most likely to benefit from nanotherapeutics, prompting the development of personalized nanomedicine.Effective systemic delivery of nanotherapeutics to solid tumours requires a deeper understanding of the biological factors involved, such as nanoparticle–protein interaction, blood circulation, extravasation to and interaction with the perivascular tumour microenvironment (TME), tumour tissue penetration, tumour cell internalization and intracellular trafficking.The physicochemical properties of nanotherapeutics (for example, size, geometry, surface features, elasticity, stiffness, porosity, composition, targeting ligand and drug release kinetics) affect systemic delivery to tumours, thus determining the EPR effect and therapeutic outcomes.Targeting the TME and the premetastatic niche with nanotechnologies offers another promising strategy for cancer therapy.Addressing the challenges of controllable, reproducible and scalable nanoparticle synthesis will facilitate the clinical translation of cancer nanomedicines.