The evolution of tumor-targeted drug delivery: From the EPR effect to nanoswimmers

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 Skepticism has been replaced by the understanding that precision at the nanoscale allows improved treatment modalities in humans.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, drugproducing, bacteria. Interestingly, sperm may be nature's best example of a multifunctional, targeted, high-fidelity, self-propelled, delivery system that we can learn from.