Engineering long-circulating nanomaterial delivery systems.

One of the grand challenges at the forefront of bionanomaterials is their quick clearance in blood circulation. Progress has been made in understanding nanomaterial-biological system interactions and in developing new strategies to extend the blood circulation time of nanomaterials. Here, we first review interactions between the complement system and nanomaterials as well as clearance pathways in major organs such as the liver, spleen, and kidneys. We then discuss new approaches to prolong the blood circulation of nanomaterials with a focus on grafting polymers and biomimetic camouflages including cell membrane coating and hybrid vesicles. In the end, we provide insights into the pros and cons of these approaches and our perspectives for advancing this field.