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  • br It is obvious that precision diagnostics should be


    It is obvious that precision diagnostics should be considered as the necessary premise for the development of precision therapies. A 2009 report by The Lewin Group, one of the largest health care pol-icy research groups, estimates that laboratory diagnostics account for less than 5% of hospital costs and about 1.6% of all Medicare costs while laboratory test results have as much as 60–70% impact on the health care decision-making [20].
    Overall, to successfully treat cancer patients, scientists need to develop precision diagnostics that would be accurate and reliable. With regular access to screening programs and early diagnosis, patients would have immediate access to treatments that may lead to better outcomes. Within this framework, the emerging field of the nanobiointeractions may pave the way to success of precision diagnostics.
    NanobioInterfaces:a challenge to therapeutic and diagnostic nanotechnology
    For more than two decades, grafting polymers such as polyethy-lene glycol (PEG) [21,22] to nanocarriers’ surface has been considered as a new drug delivery option for cancer patients and represented one of the greatest opportunities for the cancer market (e.g. stealth liposomal drugs [23]). Researchers and phar-maceutical companies have recognized that modification of the PEG-molecule terminus with targeting ligands could produce ideal nanodevices for targeted delivery of nanomedicines [24,25]. Some targeted products developed by pharmaceutical companies have shown promise but have not exceeded the level of development and are not commercially available [26]. This failure and the loss of financial support for development of innovative nano-biomedical based drug delivery systems and devices, prevented researchers to overcome their limited understanding of the biological behavior of nanomaterials exposed to physiological environments. Recently, the scientific Liproxstatin-1 has started to unravel several “hidden fac-tors” existing at the interface between nanomaterials and biological systems [16,27]. We now know that as soon as functionalized NPs are exposed to a biological environment such as body fluid, their surface is immediately covered by biomolecules present in the media resulting in formation of biomolecular corona (BC) that
     evolves mainly quantitatively over time with small qualitative vari-ations [28,29] and is influenced by physico-chemical properties of the NPs [30], the source of biomolecules (e.g. plasma vs. serum [31]; human plasma vs. mouse plasma [32]), media concentration [30,33] as well as temperature [34], flow dynamics [35] and expo-sure time [36]. A turning point was achieved when researchers discovered that grafting PEG and other polymers to the surface of NPs does not completely preclude adsorption of plasma pro-teins [37] making the surface of nanomaterials inaccessible to the interaction with the medium exposed. The interaction of the NPs with cellular and extracellular components take place through the protein present in BC formed on the surface of the NPs [36]. More-over, a recent study [38] demonstrated that PEG can also affect the composition of the corona preventing non-specific cellular uptake. As a result, it is clear that most targeted nanomaterials can lose their targeting capabilities in a physiological environment and acquire potentially unpredictable functionalities [15]. There are several proposed approaches (e.g., using zwitterionic coatings [39,40]) that can reduce the masking effects of protein corona [27]. Thus, designing innovative functionalized NPs could potentially be an efficient method for developing targeted corona-covered nano-materials with reduced adverse effects produced by the random nonspecific corona. Formation of protein corona can also affect immune system response which may influence the safety and effi-cacy of the diagnostic/therapeutic nanoparticles [41–43].
    The overlooked aspects of nanomedicine demand the review of many previous discoveries and experiments performed in vivo. On the other hand, because corona formation is inevitable and may vary in different people, it could be explored for develop-ment of safe and efficient nanotechnologies. Indeed, the possibility of controlling the composition of corona could enable new excit-ing opportunities in ’camouflaging’ a nanomaterial, e.g. mitigating toxicity and directing biodistribution. Hajipour et al. [44,45] have demonstrated that patients with various diseases, including can-cers exhibit personalized coronas that evolve over time with disease progression. For example, corona could trigger variable cellular processes relevant to efficacy of drug treatment such as controlled release, production of reactive oxygen species, lipid per-oxidation and apoptosis.