Preclinical evaluation in mice of nanobioconjugates against colorectal cancer: follow-up in vivo by tomography (pet-ct) of the adenocarcinomatous process and its control.

Colon and rectal cancer commonly known as colorectal cancer (rcc) is the third most common type of cancer worldwide and ranks fourth when it is classified according to mortality (globocan-iarc 2012). in accordance with the global epidemic, in colombia, through resolution 0247 of 2014, the registration of the information of patients with cancer began, from this first report a record of 139,789 cases was obtained in the country; breast cancer was the one with the highest number of registrations with 33,095 cases followed by prostate cancer with 14,350 cases and cervical cancer 12,618 cases, in fourth place and being the first type of cancer relevant for both sexes, colorectal cancer was located with 8,824 cases (pointet et al 2017, ins 2015). despite the advances in technology for diagnosis and treatment, we see how its incidence continues to increase (donovan et al 2016), due to this in recent years there has been a great interest in seeking other treatment or improvement strategies among those that stand out: i) the chemical synthesis of new phytochemical analogs to increase efficacy and bioavailability, based on the design of hybrid molecules; ii) new formulations and phytochemicals to selectively deliver to the target organ through the use of nanotechnology or nanochemistry prevention; iii) the use of animal models to evaluate response to new treatments as proposed below and is the focus of this proposal. taking into account the above, the objective of this project is to determine by radiological, immunological and histopathological methods, the anticancer capacity that would have two nanotransporters charged with natural, synthetic or functionalized hybrid molecules with specific antibodies, in an experimental model of induced colon cancer by axo in mice. among the advantages that have been described and argue in favor of the use of the carcinogenesis model in mice, we can mention: potency, reproducibility, simplicity and similarities with human colon carcinogenesis, such as the location of tumors that are concentrated in mice and humans in the distal part of the colon. here it is important to highlight that, although the "gold standard" for the phenotypic analysis of a murine model of cancer is histology, it implies the sacrifice of a certain number of animals. in this sense, in an attempt to change these conditions in the future and as a novelty in the project, we propose, parallel to histopathological studies, to evaluate the use of non-invasive tools such as pet positron emission tomography as a valid tool for visivilization and quantification in vivo of the carcinogenic development process in mice. pet provides the means to measure the rates of biological processes using radioisotope-labeled molecules that emit posotrons. the most commonly used labeled pet probe is 18f-fdg, which allows the evaluation of glycolysis disorders associated with malignant transformations in cells. colon cancer during its development markedly increased glycolysis rates and, consequently, pet 18f-fdg shows high sensitivity and specificity in the initial diagnosis and stratification of this type of neoplasia (seam p et al 2007). recently, different studies have been published in which the opportunity exists to use this type of different types of cancer, which are evaluated in vivo by using pet for small animals such as conventional pet-ct (walter ma et al 2010) .

To determine, by radiological, immunological and histopathological methods, the anticancer capacity of two functionalized nanotransporters for therapeutic treatment in an experimental mouse colorectal cancer model. specific objectives to optimize the use of conventional tomography (pet-ct) for application in small animals such as the mouse, standardizing a protocol that allows obtaining images with diagnostic quality to reliably and reproducibly assess the changes occurred during the development and treatment of the colon adenocarcinoma. to determine the hispatological changes during the development and treatment with nanotransporters of colorectal cancer in mice. follow up in vivo by tomography (pet-ct) of the anticancer capacity of two functionalized nanotransporters for the treatment of colorectal cancer initiated in studies of polyposis, adenoma and carcinoma. to determine the immunomodulation (expression and methylation) of different relevant markers involved in apoptosis, cell cycle and immune response processes during the development and treatment with nanotransporters of colorectal cancer in mice.