Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance.

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Therapeutic nanotechnologies have made great progress over the past decade. Skepticism has been replaced by the understanding that precision at the nanoscale allows improved treatment modalities in humans. Principles for designing tumor‐targeted drug delivery systems are described. At first, the enhanced permeability and retention (EPR) effect was the major targeting mode, with up to 10 % of the injected dose actually reaching tumors. To improve cellular uptake, sugars, antibodies, peptides or other ligands were added to the surface of nanotherapeutics. These can be coupled with external magnetic fields or ultrasonic waves to propel iron oxide or gas‐filled particles towards the disease site. Next‐generation drug delivery systems will be capable of autonomously swimming towards the disease site and penetrating deep tissue, independent of blood or lymphatic flow. This has been shown to some extent with modified, drug‐producing, bacteria. Interestingly, sperm may be nature’s best example of a multifunctional, targeted, high‐fidelity, self‐propelled, delivery system that we can learn from.