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.

Pharmacokinetic Analysis of Peptide-Modified Nanoparticles with Engineered Physicochemical Properties in a Mouse Model of Traumatic Brain Injury

“…Biodistribution and passive tumor accumulation of micelles modified with anionic aspartic acid or cationic lysine residues mediated by the enhanced permeation and retention (EPR) effect were affected by nanoparticle charge in a mouse model of ovarian cancer ( 21 ). Passive nanoparticle accumulation into the brain after TBI via the dysregulated BBB post-injury has been compared to the EPR effect in solid tumors ( 10 , 11 , 22 , 23 ), suggesting that the physicochemical properties of peptide-modified nanoparticles may also affect nanoparticle passive accumulation in the injured brain after TBI. To our knowledge, there has not yet been a systematic study of how the physicochemical properties of peptides displayed on nanoparticle surfaces affect the pharmacokinetics of nanoparticles in a mouse model of TBI.…”

Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery

“…The particular advantages of drug delivery systems in brain injury include that (i) blood-brain barrier permeability for a specific drug is substantially increased, (ii) drug delivery can be targeted selectively to sites at risk of injury, (iii) these systems carry the potential of gradual drug release to elongate drug exposure, and (iv) local drug concentration may become high enough to exert therapeutic effect, without the risk of drug accumulation in non-target tissues, which carries the risk of undesirable side effects or off-target toxicity. “Smart” nanonsystems may meet all these requirements, and provide an effective tool in the management of ischemic stroke [ 29 , 30 ].…”

The Peptide Functionalized Inorganic Nanoparticles for Cancer-Related Bioanalytical and Biomedical Applications

“…Diagnostic and therapeutic agents play critical roles in the combat against this malignant disease. Because of their unique physicochemical properties such as large specific surface area, easy functionalization, and excellent optical, electrical, and magnetic properties, a variety of inorganic nanoparticles (NPs) have been extensively studied for early detection and treatment of cancers since 1996 [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. For instance, due to their morphology (size, shape, and structure)-dependent localized surface plasmon resonance (LSPR), colloidal gold NPs (AuNPs) have been employed for the development of simple colorimetric sensing systems for sensitive detection of various cancer-related biomarkers and carcinogens [ 2 , 3 , 4 , 9 , 10 , 11 , 29 ].…”

“…Magnetic nanoparticles such as iron oxide NPs (IONPs) are excellent theranostics for magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) against cancer because they exhibit good biocompatibility, strong magnetic resonance (MR) contrast capacity, and high photothermal conversion efficiency [ 12 , 13 , 14 ]. In particular, the NPs prefer to accumulate in tumor sites by the size-dependent enhanced permeability and retention (EPR) mechanism [ 21 , 28 , 30 , 31 , 32 ]. This beneficial combination of physical and chemical properties has also given rise to an important application of NPs in the delivery of different anticancer drugs including traditional chemical drugs, small-interfering RNA (siRNA), and antigens [ 7 , 16 , 28 , 30 , 31 ].…”

“…In particular, the NPs prefer to accumulate in tumor sites by the size-dependent enhanced permeability and retention (EPR) mechanism [ 21 , 28 , 30 , 31 , 32 ]. This beneficial combination of physical and chemical properties has also given rise to an important application of NPs in the delivery of different anticancer drugs including traditional chemical drugs, small-interfering RNA (siRNA), and antigens [ 7 , 16 , 28 , 30 , 31 ].…”