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  • br ing a game changerin advancing cancer


    ¨ ing a game¨ changerin advancing cancer diagnosis. This is the case, for instance, for nanoparticle (NP)-based imaging that will likely provide superior diagnostic and prognostic information that is otherwise difficult to obtain, potentially advancing personalized clinical care.
    Diagnostic vs. Therapeutic technology in the emerging field of precision health
    It is well known that response to external stimuli differs among individuals and that patients with the same condition show differ-ent sensitivity and therapeutic response to the same drug. The term ¨ precision¨ medicinehas now been used with increasing frequency to indicate a new approach to medicine in which patient’s individual
    G Model
    variability plays a major role [15]. Many biological factors [16] such as cell type, cell size, cell sex and the varying complexity of tumor microenvironment play a key role in determining the heterogeneity of a given cancer leading to patients’ P22077 in response to drugs. Among these factors, continuously changing tumor microenviron-ment with its spatial and temporal heterogeneities can seriously impact the outcome of cancer treatment [17].
    While efforts have been made at advancing new cancer ther-apeutics on the market, much less focus has been directed to precision monitoring and diagnostics, i.e. to the tools that are nec-essary to predict, prevent or identify the disease early. As has been emphasized by Dr. Sanjeev Sam Gambhir (Stanford University), the focus of health care has to shift from “precision medicine” to “precision health”, which would provide customized monitoring to healthy individuals, identify those at risk early and timely detect any signs of malignancy [18]. The availability of these tools would reduce the overall treatment costs and dramatically improve the outcome. However, today’s diagnostic tools are not at the forefront of modern oncology even though precision molecular diagnostics called companion diagnostics are among mandatory prerequisites for the beneficial use of the targeted drugs [19]. For example, without precise laboratory diagnosis of the V600E mutation in melanoma or HER2 amplification in breast cancer, there would be no benefit for the patients to be treated with the drugs against these markers in addition to unjustifiable financial burden to the healthcare systems.
    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 community 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 P22077 corona can also affect immune system response which may influence the safety and effi-cacy of the diagnostic/therapeutic nanoparticles [41–43].