Seite - 119 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Clift et al. Theranosticnanoparticlesand thebloodstream to the specifically chosen target site (Davis et al., 2008). Therefore it is essential that the interpretation of the effectiveness of theranostic NPs directly upon the target site isconsideredaftergainingacontrolled understanding of the biological impact upon the NPs following their transport throughdifferentbiological environments tosaid target site. Thus, in order to fully elucidate the impact of the transport processes fol- lowing administration of theranosticNPs untilreachingtheirtargetsite,comprehen- sion as towhat biological entities interact with theNPs, how their physico-chemical characteristics may be altered over time and from interaction with different envi- ronments, as well as subsequently how these potential adaptations might affect the effectiveness of the NPs when they engagewith the intended siteof interest is decidedlynecessary. Focusupon thesekey aspectswouldfurtherenabletheenhanced development of theranostic NPs from a materials’ perspective, allowing them to be optimized formaximal benefit toward their proposed application. Through this approach, significant improvement to the efficacyof theNPs to the target sitewould be obtained concomitantly. Nonetheless, whichrouteof transport toward the target site of the applied theranosticNPs should bestudiedfirst? APPROACHINGTHEPROBLEM The main administration route for most theranostic-based NPs is via intra- venous injection (Nichols andBae, 2012). Thus, the initial biological environment that these theranostic-based NPs will encounter is the complex cellular and molecularmilieuof thehumanbloodcir- culation (as described inFigure1). Thus, foremost direction toward understand- ing its impact upon theranostic NPs is paramount. To systematically study the impact of the bloodstream upon thernostic NPs, in vivo (i.e., rodents) assessment would rapidly determine the efficacy of NPs formulated for theranostics. Yet, despite encompassing a “whole-body” scenario, it would not provide species specificity, which would be necessary for the inevitable application of NPs as theranostic agents. Primates would therefore be ideal, as used in the study by FIGURE1 |Schematicofahumanbloodvessel, representativeof thehumanbloodstream. Imageshows the threemaincell types, (i) erythrocytes, alsoknownas redbloodcells (RBCs) (represented asflat, disc-shaped red cells),whichcontainhemoglobin (an iron-containing biomolecule responsible foroxygen (O2)binding), (ii) leukocytes (i.e.,whitebloodcells) (represented aswhite, round cells) and (iii) thrombocytes (i.e., platelets) (represented assmall purple cells), theessential cell type that allows forbloodclotting (AbbasandLichtman,2003). The humanbloodstream is responsible for thecirculationofnutrients (i.e., aminoacids),O2 and hormones, inaddition to the removal ofmetabolicwaste (e.g., carbondioxide) (Abbasand Lichtman,2003). It assists in regulatingbody temperatureandpH,and furtherengages in the fightingofdiseasestates.All of these functionscontribute toward theessentialmaintenanceof the homeostasisof thehumanbody. Inaddition thehumanbloodstream issuspendedwithinaprotein matrix, abundant inalbumin, knownasplasma (i.e., bloodserumtogetherwithfibrinogens) acting under the influenceofnon-classical hydrodynamicflow,knownashaemodynamics (Abbasand Lichtman,2003). Thesuitabilityof thisholisticenvironmentuponnanoparticles (represented as gold spheres) for theranostic applications iscurrently limited. Ye et al. (2012), who showed the applica- bilityofquantumdots asuseful theranos- tic tools.However, neither in vivo strategy would provide the basis for a systematic study as to how NPs may interact with their numerous local environments (i.e., within the bloodstream) prior to arriving at their intended target site in the human body. By adopting an in vitro perspec- tive however, itwould enable a controlled outlook toward studying the impact of each biological constituent of the human bloodstream upon the chosen theranos- ticNPs.Difficulties in this approach arise however, since it would only allow for monoculture, or, at the most, co-culture systems tobeused to conduct such inves- tigations. Although advanced in vitro sys- tems concerning the bloodstream and its constituent parts are being established, suchastheadvancedplateletmodelsystem recently reported byThon et al. (2014), a finitemodelsystemthatmimicstheblood- stream is currently lacking. Therefore, currently, to comprehend how biological environments, such as the bloodstream, mayimpactupontheeffectivenessof ther- anosticNPsacombined invitroand invivo approach should be integrated as a vital component in the development of thera- nosticNPs. On an additional note, it is prudent to note that such a systematic study of any therapeutic NPs from the specific expo- sure site, via the potential transport route to the target site should be performed in order to gauge their potential effec- tiveness following administration. In this Frontiers inChemistry | ChemicalEngineering February2015 |Volume3 |Article7 | 119