Nanomedicine for Acute Brain Injuries: Insight from Decades of Cancer Nanomedicine

Abstract

Acute brain injuries such as traumatic brain injury and stroke affect 85 million people a year worldwide, and many survivors suffer from long-term physical, cognitive, or psychosocial impairments. There are few FDA-approved therapies that are effective at preventing, halting, or ameliorating the state of disease in the brain after acute brain injury. To address this unmet need, one potential strategy is to leverage the unique physical and biological properties of nanomaterials. Decades of cancer nanomedicine research can serve as a blueprint for innovation in brain injury nanomedicines, both to emulate the successes and also to avoid potential pitfalls. In this review, we discuss how shared disease physiology between cancer and acute brain injuries can inform the design of novel nanomedicines for acute brain injuries. These disease hallmarks include dysregulated vasculature, an altered microenvironment, and changes in the immune system. We discuss several nanomaterial strategies that can be engineered to exploit these disease hallmarks, for example, passive accumulation, active targeting of disease-associated signals, bioresponsive designs that are "smart", and immune interactions.

Keywords: Nanomedicine; engineering design; stroke; traumatic brain injury.

Figure 1.. Nanomaterial paradigms in acute brain injury.

Nanomaterials can be engineered to respond to disease physiology in acute brain injuries, including dysregulated vasculature (pink), an altered microenvironment (gray and blue), and changes in the immune system (yellow). Specific examples for each nanomaterial design can be found in Table 1, color-coded by quadrant.

Figure 2.. Nanomaterials that interact with vasculature in cancer and acute brain injury.

a, b. In cancer and acute brain injury, nanomaterials can (1) passively accumulate into adjacent tissue, (2) actively target cells in the tissue, (3) target upregulated receptors on endothelium, and (4) target clots. c, d. Dysregulated vasculature in cancer and acute brain injury allow for passive accumulation of nanomaterials in the diseased tissue.