Bimodal silver nanoparticles modified with targeted biocompatible chitosan polymer for intelligent colon cancer theranostic
Bimodal silver nanoparticles modified with targeted biocompatible chitosan polymer for intelligent colon cancer theranostic
Fatemeh Mahboubi,1Javad Mohammadnejad,2Sepideh Khaleghi,3,*
1. Department of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2. Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, Iran. 3. Department of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Introduction: Colorectal cancer is the third most common cancer worldwide, the second leading cause of cancer-related death, and the leading cause of death from gastrointestinal cancer. The lack of early detection methods is one of the main reasons for the high mortality rate caused by this disease. Conventional imaging techniques are incapable of distinguishing benign tissue from malignant tissue, resulting in misdiagnosis or late-stage diagnosis. Therefore, the development of novel technologies to diagnose colorectal cancer accurately and promptly minimizes mortality from the disease. Surface-enhanced Raman spectroscopy (SERS) is one of the most precise techniques for molecular imaging, with advantages, such as non-invasion, high sensitivity, and specificity. Silver nanoparticles improve Raman spectroscopy signals due to the intensification of surface plasmons. Nanoparticle stability can be enhanced by adopting the Metal-Organic Framework (MOF). Due to numerous structural topologies, highly specialized surfaces, and ordered crystalline pores, MOFs are the appropriate choice for fixing metal NPs. Our aim in this project is the synthesis of Chitosan decorated MOF-Silver nanocomposites conjugated with folic acid for targeted diagnosis of colon cancer by Surface-enhanced Raman spectroscopy (SERS).
Methods: Silver nanoparticles were synthesized by the green method using cyanobacterium spirulina extract. The synthesized silver nanoparticles were attached to the Metal-Organic-Framework (MOF) by different methods. The physical and chemical properties of nanocomposites were investigated using TEM, SEM, and XRD imaging methods that evaluate the morphology of nanocomposites. The hydrodynamic size of nanocomposites was determined by the DLS test. The surface charge of nanocomposites was evaluated by zeta potential test. Chitosan was conjugated with folic acid and the accuracy of covalent bonds and interactions in nanocomposites at each step was confirmed by the FTIR method. The crystal structure of nanocomposites was evaluated by the XRD method. Raman signals of nanocomposites were analyzed by Raman spectroscopy. The toxicity of MOF@Silver nanocomposite at different concentrations of MTT treatment on HCT116 colon cancer and HGF human normal cell lines was also evaluated. Finally, the results will be evaluated with SPSS software and t-test and one-way ANOVA.
Results: According to the findings of a morphological investigation, chitosan nanoparticles targeted with folic acid have an appropriate size and a spherical appearance. The crystallized structure of nanocomposites was evaluated by XRD. The covalent attachment in MOF structure and the confirmation of silver nanoparticle synthesis were assayed by FT-IR. The Surface-enhanced Raman spectroscopy of MOF@Silver nanocomposites which is synthesized by different methods shows different signaling abilities according to the process of preparation. The MTT assay was used to demonstrate the lethality of this nanocomposite in HCT116 colon cancer and HGF human normal cell lines. The application of folic acid-targeted chitosan-coated MOF-Silver nanocomposite modifies Raman spectroscopy signals dramatically, and it is toxic to colon cancer cells (HTC116). However, the cytotoxicity of Folic acid targeted MOF-Silver-chitosan nanocomposites is reduced in face of human normal HGF cell line.
Conclusion: SERS (Surface Enhanced Raman Spectroscopy) is a beneficial and safe method for detecting biological targets like cancerous cells. We show that a folic acid-conjugated, Raman-labeled chitosan MOF@Silver nanocomposite can be used to identify folate receptor positive colon cancer cells in this study. Moreover, the nanocomposites have acceptable biocompatibility against normal cell line. Nanoparticle-based Surface Enhanced Raman Spectroscopy (SERS) analysis offers a lot of potential for accurate colon cancer diagnosis, and it could help save a lot of colon cancer patient's lives throughout the world.