Nanoparticle

Materials science

Blood circulation

Computer science

Drug delivery

Nanotechnology

Nanomedicine

Nanocarriers

Internal medicine

Cancer therapy

Medicine

Site of action

Cancer

Traditional medicine

Frontiers in Bioengineering and Biotechnology

The exploitation of nanosized materials for the delivery of therapeutic agents is already a clinical reality and still holds unrealized potential for the treatment of a variety of diseases. This review discusses physiological barriers a nanocarrier must overcome in order to reach its target, with an emphasis on cancer nanomedicine. Stages of delivery include residence in the blood stream, passive accumulation by virtue of the enhanced permeability and retention effect, diffusion within the tumor lesion, cellular uptake, and arrival at the site of action. We also briefly outline strategies for engineering nanoparticles to more efficiently overcome these challenges: Increasing circulation half-life by shielding with hydrophilic polymers, such as PEG, the limitations of PEG and potential alternatives, targeting and controlled activation approaches. Future developments in these areas will allow us to harness the full potential of nanomedicine.

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?