The dawning era of anticancer nanomedicines: from first principles to application of silk nanoparticles

This review introduces nanomedicines and medical silks by addressing seminal and recent research within these fields. First, successes of nanoparticles in improving the safety profiles and pharmacokinetic-pharmacodynamic properties are explored but also the concepts of threshold dosing and targeting of tumor-associated macrophages. Current barriers to systemic delivery of nanomedicines are detailed and methods to overcome these barriers and increase tumor targeting are evaluated, namely: tuning the nanomedicine size and surface charge for enhanced tumor accumulation and penetration; non-spherical nanomedicine morphologies for macrophage evasion and targeted delivery to endothelial cells; and, surface functionalization for stealth coatings and targeting receptor-mediated endocytosis. We discuss the advantages of using silk as a nanomedicine with reference to its structure, composition, biological performance and formulation. While batch methods for silk processing have enabled the formation of nano to microparticles, continuous technology can overcome bottlenecks of the deployed engineering methods such as low throughput and poor reproducibility. Finally, the chemical modification of silk using homogeneous and heterogenous chemistries is assessed within the nanomedicine context. Overall, this review covers silk nanomedicines from first principles to carrier design and on to areas of future development.