br The overlooked aspects of nanomedicine
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.
Combination of these findings have formed a new paradigm postulating that the interaction between the nanomaterial and bio-logical fluid could create a nanobiointerface leading to a formation of a specific biomolecular corona, which could be responsible for different personalized responses to drug treatments and, in turn, for many failures of clinical trials. Now, researchers need to develop a more in-depth understanding of the interaction between NP sur-face and macromolecules, in particular proteins within the corona. However, considering that personalized corona will impact target-ing capability of the drug, the outcomes will differ from patient to patient. Therefore, to exploit the corona for targeted drug delivery it is essential to design customized NPs for cancer patients with sim-ilar proteomes which may cause difficulties in commercialization of these materials .
On the other hand, NPs containing a specific corona could be designed to develop safe, user-friendly and cheap methods for cancer diagnostics. Upon exposure to patient serum, NPs could ¨ function as a nano¨-concentratorfor specific proteins with affinity to a specific surface of NPs. Alteration in the BC composition has already been exploited for developing of a liposome-blood test for early detection of PDAC , which was able to discriminate between healthy individuals and pancreatic cancer patients with a total correctness rate of 88% . Recent research suggested that BC composition is also influenced by tumor size and presence of distant metastases in PDAC , though it needs to be confirmed on larger cohorts. In another study, characterization of the protein corona formed around lipid NPs upon exposure to plasma proteins
allowed for identifying patients with meningeal tumors thus open-ing a new door for early diagnosis of (±)-Baclofen cancer . Extensive investigations are necessary to validate clin-ical applications of BC-based blood tests, and to rigorously evaluate the factors that may influence their specificity and sensitivity.
Lastly, we expect that by comparing corona profiles of cancer patients and healthy individuals, new insights on the biology and stage of many types of cancer may be generated. This is a key issue that is attracting increasing interest and deserves further investi-gation in the future.
Conclusions and recommendations
Over the last decade, nanotechnology has provided researchers with the unprecedented opportunity to manipulate nanomateri-als to generate entirely novel therapeutic and diagnostic agents for cancer patients. However, as in any other field of science, advance-ments in cancer research are strongly related to availability of funding. Today, financial support coming from the government is often inadequate and an increasing flow of money is coming from big private firms that dominate the market. But, business models of big pharmaceutical companies aim at accumulating drugs in the pipeline rather than developing companion diagnostic tools. How-ever, such tools could be vital for development of highly effective therapeutics for cancer patients.
A turning point in the development of new technologies for cancer diagnosis will come from the exploitation of the biomolecu-lar corona that surrounds nanomaterials in vivo. BC-enabled blood tests can provide early detection of cancer with high sensitivity and specificity, allowing scientists to detect minor changes in plasma proteins even at a very early stage of disease. Development of these technologies is still in its infancy, but investigation of BC can add new knowledge to the quest in earlier disease detection.
Finally, we personally believe that the field is in desperate need of researchers, venture capitalists, entrepreneurs, and media advo-cates who are either extraordinarily empathetic, or whose lives have been directly affected by these devastating diseases . We imagine a large, well-organized movement, motivated not by wealth or fame, but by a wholehearted commitment to changing the course of the healthcare through improving early diagnosis and treatment of disease and relieving the suffering of both patients and their families. Absent such a movement, we should expect to see the continued failure of early disease detection combined with sub-stantial increase in the prevalence and incidence of diseases, as they evolve and acquire resistance to current therapeutic approaches. History teaches that even a few people like Leroy Edgar Burney (who was the first to publicly identify tobacco as a cause of lung can-cer) and Rachel Carson (who combated pesticides as a cause of bird population decimation), can change the course of the world for the better. We call upon funding agencies, researchers, entrepreneurs, and media to help re-balance the energy/funding disparity between diagnostic and therapeutic efforts. We believe this will set the stage for a dramatic cost reduction in the medical field, ultimately pro-tecting patients from catastrophic diseases and their families from both emotional and financial duress.