Document Type: Conference Proceedings
Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Iran
Department of Chemistry, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
Pharmaceutical Department, Food and Drug Laboratory Research Center, Food and Drug Organization (FDO), Ministry of Health, Tehran, Iran
Introduction: Noninvasive magnetic resonance imaging (MRI) and targeted drug delivery systems, usually referred to as theranostic agents, are being developed to enable detection, site-specific treatment, and long-term monitoring.
Materials and Methods: To elucidate the effects of coating on cellular uptake and biodistribution of nanoparticles (NPs), negatively charged Fe-MIL-88B-NH2 (MIL-S) was developed and loaded by curcumin (CUR). After that, chitosan (CS) was conjugated to folic acid (FA). Then MIL-S─CUR was coated by CS targeted by FA (FC) and partially negatively charged MIL-S─CUR@FC was developed.
Results: MIL-S and MIL-S─CUR@FC owned Zeta potentials of -23 and -2 mV, respectively. MTT assay showed MIL-S─CUR@FC could have maximum cell toxicity on cancer cells due to partially negative charge and active targeting. In vivo magnetic resonance imaging (MRI) images suggested that liver uptake was very high for negatively charged MIL-S. The high T2 contrast effect of MIL-S in liver is likely due to active phagocytosis by macrophages (Kupffer cells) in the liver. In contrast, liver uptake was very low, but tumor uptake was very high for MIL-S─CUR@FC showing high dual contrast (T1/T2). The pH-responsive behavior of MIL- S─CUR@FC in tumor tissue made it dual T1 /T2 contrast agent by decomposition of NPs.
Conclusion: It could be concluded that coating, active targeting, and reducing the surface charge of MIL-S─CUR@FC reduced the undesirable clearance by the reticuloendothelial system (RES) such as liver. On the other hand, the anti-cancer drug delivery improved more efficiently to the tumor sites and maximized therapeutic efficacy and predictable in vivo properties. Here described a pH sensitive MRI NPs, may serve as a useful theranostic agent for cancer diagnosis and treatment.