Seite - 118 - in Cancer Nanotheranostics - What Have We Learnd So Far?

OPINIONARTICLE published:10February2015 doi: 10.3389/fchem.2015.00007 Abiologicalperspective toward the interactionof theranosticnanoparticleswith thebloodstream–what needs tobeconsidered? MartinJ.D.Clift1*, Jean-FrançoisDechézelles1,BarbaraRothen-Rutishauser1 andAlkePetri-Fink1,2 1 BioNanomaterials,Adolphe Merkle Institute, Universityof Fribourg, Fribourg, Switzerland 2 Department ofChemistry, Universityof Fribourg, Fribourg, Switzerland *Correspondence: martin.clift@unifr.ch Editedby: João Conde, Massachusetts Institute ofTechnology, USA Reviewedby: Matthew Samuel Powys Boyles, Salzburg University,Austria Keywords:blood,bloostream,nanomedicine, redbloodcells,whitebloodcells,platelets, invitro Nanomedicine intends to create and fur- ther use novel materials at the nanoscale in order to provide an improvement upon current medical applications for human healthcare (ESF, 2005; Etheridge et al., 2013). In line with the advances made within nanotechnology since the late twentieth century (Mamalis, 2007) nanomedicine has received heightened attention due to its potential advantages, mostnotablywithin (cancer) theranostics (Muthuetal.,2014).Thefieldoftheranos- tics aims to utilize the physico-chemical characteristics of nanosized materials in order to intensify the effectiveness in diagnosing and treating diseases at the molecular level (Kim et al., 2013). Such a perspective is notably paramount for cancer types that are difficult to iden- tify as well as apply therapy toward (e.g., secondarycancer) (Muthuetal., 2014). Despite thewell documented andpro- posedbenefitsof therapeutics inthenano- size range (Krol et al., 2013), for the majority of nanoparticles (NPs) [defined as “a nano-object with all three dimen- sions in the nanoscale (1–100nm)′′ (BSI, 2007; ISO 27687, 2008)], the ability to mergetheexpansivedividebetweendevel- oping a significant advancement within material science and creating a biologi- cally relevant therapeutic has proven to be a highly non-trivial task. One impor- tant reason for this is the relatively limited specific understanding of the biological interaction of therapeutic NPs following their administration into thehumanbody andtheir subsequentdelivery to the target site (e.g., tumor)(CapcoandChen,2014). Theobjectiveof thisopinionarticle there- fore, is to provide a biological perspec- tive uponwhatmust be considered in the developmentof theranosticNPs. WHERESHOULDFOCUSBEGIVEN? For biologically effective theranostic NPs, determining their dispersity, bio- compatibility and biostability within different biological environments is imperative. For this, an understanding of the dynamic interaction between NPs with liquid and cellular systems as well as their subsequent biological impact must be gained. This outlook is not straight-forwardandrequiresanintensive, multi-interdisciplinaryresearchfocuswith cross-talk/feedback loops between the material scientists developing the mate- rials and the biologists/clinicians wishing tostudy/apply them. Initially, from a material perspective, thereareanabundanceofcomplexhurdles that must be overcome when developing anyproposednanotheranostic(Petrosand DeSimone, 2010). Whether the NPs are manufactured for use as a treatment e.g., degenerativediseasestates(e.g.,Alzheimer disease) (Liu et al., 2005), infectious dis- eases (e.g., hepatitis B) (Li et al., 2010) cancer (McMillan et al., 2014), or as a diagnostic tool (Niemirowicz et al., 2012), a systematic chemistry approachmust be used (Davis et al., 2008).Whilst the spe- cificshapeof theNPsisofextremeinterest regarding their efficiency as a theranostic agent (Liu et al., 2012), it is the precise material applied that is important, aswell as the surface layer and the subsequent surface attachment of therapeutic agents and additional molecules (e.g., fluo- rophores, receptor-targetting moieties) to the modality (Petros and DeSimone, 2010), while keeping within the nano- size range.Additionally, determining their dispersity (i.e., colloidal stability) and biostability can also be laborious and problematic(PetrosandDeSimone,2010). Although these issues arenot trivial, once theNPisengineeredandreadyforuse,one of the main, biologically-based obstacles is to determine the ease of directing this modality to the site of interest within the human body without causing any unde- sirable effects (e.g., recognition and/or clearancebythe immunesystem). Successful targeting of theranosticNPs is an onerous concept (Nicolaides et al., 2014), and is commonly overlooked in favor of immediately focussing upon the effectivenessof the theranosticagentupon the specific target site (i.e., cancer cells for cancer therapeutics) (Xie et al., 2011). For example, a plethora of studies have been publishedwhichhave showntheeffective- nessof theranosticNPs ineither thedeliv- ery of a drug to cells (Najafi et al., 2014), or destructing cancer cells with or with- out external stimuli (e.g., light, magnetic field) (Hayashietal., 2014).Naturally, this approach is of extreme importance, and absolutely vital toward the development of any theranostic based NPs. However, the precise effective nature (i.e., efficacy) of the NPs upon the chosen target site canbeconsideredas inextricably linked to the efficient transport of NPs from their administration site into the human body www.frontiersin.org February2015 |Volume3 |Article7 |118