RESUMO
More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.
Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Ciclosporina/administração & dosagem , Portadores de Fármacos/efeitos da radiação , Fármacos Neuroprotetores/administração & dosagem , Fotoquimioterapia/métodos , Animais , Carbocianinas/química , Carbocianinas/efeitos da radiação , Ciclosporina/farmacocinética , Modelos Animais de Doenças , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos da radiação , Humanos , Raios Infravermelhos , Nanopartículas/química , Fármacos Neuroprotetores/farmacocinética , RatosRESUMO
Traumatic brain injury (TBI) is a common and prevalent condition that affects large numbers of people across a range of ages. Individuals engaging in physical activities and victims of accidents are at a higher risk for TBI. There is a lack of available treatment specifically for TBI. Given the difficulty to determine its precise location in the brain, TBI remains difficult to fully diagnose or treat. Herein, we disclose a novel strategy for directing therapeutic agents to TBI sites, without the need to determine the precise location of the TBI activity in the brain. This novel approach is based on the use of a cyanine dye nanocage carrying Gabapentin, a known TBI therapeutic agent. Upon exposure of the cyanine nanocage to near-infrared light, the local release of Gabapentin is triggered, selectively at the TBI-affected site.