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Abstract
<p class="first" id="P1">Brain injuries affect a large patient population with major
physical and emotional
suffering for patients and their relatives and at a significant cost to the society.
Effective diagnostic and therapeutic options available for brain injuries are limited
by the complex brain injury pathology involving blood brain barrier (BBB). Brain injuries,
including ischemic stroke and brain trauma, initiate BBB opening for a short period
of time which is followed by a second re-opening for an extended time. The leaky BBB
and/or the alterations in the receptor expression on BBB may provide opportunities
for therapeutic delivery via nanoparticles (NPs). The approaches for therapeutic interventions
via NP delivery are aimed at salvaging the pericontusional/penumbra area for possible
neuroprotection and neurovascular unit preservation. The focus of this progress report
is to provide a survey of NP strategies employed in cerebral ischemia and brain trauma
and finally provide insights for improved NP-based diagnostic/treatment approaches.
</p>
Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad((c)) nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.
Phagocytes are key cellular participants determining important aspects of host exposure to nanomaterials, initiating clearance, biodistribution and the tenuous balance between host tolerance and adverse nanotoxicity. Macrophages in particular are believed to be among the first and primary cell types that process nanoparticles, mediating host inflammatory and immunological biological responses. These processes occur ubiquitously throughout tissues where nanomaterials are present, including the host mononuclear phagocytic system (MPS) residents in dedicated host filtration organs (i.e., liver, kidney spleen, and lung). Thus, to understand nanomaterials exposure risks it is critical to understand how nanomaterials are recognized, internalized, trafficked and distributed within diverse types of host macrophages and how possible cell-based reactions resulting from nanomaterial exposures further inflammatory host responses in vivo. This review focuses on describing macrophage-based initiation of downstream hallmark immunological and inflammatory processes resulting from phagocyte exposure to and internalization of nanomaterials.
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