title: Registered bioimaging of nanomaterials for diagnostic and therapeutic monitoring.
abstract: Nanomedications can be carried by blood borne monocyte-macrophages into the reticuloendothelial system (RES; spleen, liver, lymph nodes) and to end organs. The latter include the lung, RES, and brain and are operative during human immunodeficiency virus type one (HIV-1) infection. Macrophage entry into tissues is notable in areas of active HIV-1 replication and sites of inflammation. In order to assess the potential of macrophages as nanocarriers, superparamagnetic iron-oxide and/or drug laden particles coated with surfactants were parenterally injected into HIV-1 encephalitic mice. This was done to quantitatively assess particle and drug biodistribution. Magnetic resonance imaging (MRI) test results were validated by histological coregistration and enhanced image processing. End organ disease as typified by altered brain histology were assessed by MRI. The demonstration of robust migration of nanoformulations into areas of focal encephalitis provides '"proof of concept" for the use of advanced bioimaging techniques to monitor macrophage migration. Importantly, histopathological aberrations in brain correlate with bioimaging parameters making the general utility of MRI in studies of cell distribution in disease feasible. We posit that using such methods can provide a real time index of disease burden and therapeutic efficacy with translational potential to humans.
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, USA. mboska@unmc.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Boska
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
authors.forename: Mariano
authors.initials: M
authors.lastname: Uberti
authors.forename: Balarininvasa R
authors.initials: BR
authors.lastname: Sajja
authors.forename: Shantanu
authors.initials: S
authors.lastname: Balkundi
authors.forename: Joellyn
authors.initials: J
authors.lastname: McMillan
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D018792:Encephalitis, Viral / Q000188:drug therapy / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000627:therapeutic use