ABSTRACT
OBJECTIVE: The label free ultrasmall fluorescent ferrite clusters have been engineered in a controlled fashion which was stabilized by serum protein and functionalized by folic acid for the application of targeted multimodal optical and Magnetic Resonance (MR) cancer imaging. METHODS: The ultra-small manganese ferrite nanoclusters (PMNCs) with a diameter of 4 nm have a commendable effect on the longitudinal (T1) and transverse (T2) relaxation in MR imaging that was evident from the phantom and animal MRI. RESULTS: The calculated longitudinal molar relaxivity of nanoclusters was found to be 6.9 ± 0.10 mM-1 S-1 which was exactly 2.22 times better than the conventional Gd-DOTA and their 4.01 ratio of the transverse (r2) and longitudinal (r1) relaxivities made them a potential candidate for both T1 and T2 contrast agents in MRI. In addition, the fluorescence-based small animal imaging showed folic acid driven accumulated fluorescent signal at the tumour site to conclude the capacity of PMNCs for targeted fluorescence imaging of cancer diagnosis. CONCLUSION: The cytotoxicity assay and histopathology studies were the evidence for their safe biodistribution in animal systems. Furthermore, the protein encapsulated clusters have the ability to deliver the anticancer drug Methotrexate (MTX) to the cancer tissues with a sustained manner. Therefore, one can conclude the remarkable efficacy of architect nanoclusters for theragnosis.
Subject(s)
Drug Delivery Systems , Ferric Compounds/administration & dosage , Manganese Compounds/administration & dosage , Nanoparticles/administration & dosage , Animals , Antineoplastic Agents/administration & dosage , Cell Line, Tumor , Cell Survival/drug effects , Fluorescence , Folic Acid/administration & dosage , Humans , Magnetic Phenomena , Magnetic Resonance Imaging , Male , Methotrexate/administration & dosage , Mice , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Serum Albumin, Bovine/administration & dosageABSTRACT
Magnetic resonance imaging has acquired importance as a major tool for diagnosis and staging of cancers in humans. Injection of certain imaging agents have proved to improve contrast between normal and cancer cells on magnetic resonance imaging (MRI). Using the principles of MR contrast imaging, we have designed a dual mode (T1 and T2) contrast agent based on folic acid functionalized manganese ferrite nanoparticles (MNP) entrapped in 3G polyamidoamide (PAMAM) dendrimers. The ratio of Mn:Fe was tuned to achieve optimal performance. This multifunctional nanocarrier system was developed for targeting cancer cells to produce both T1 and T2 contrast which in turn helps in better diagnosis and staging of cancer. FTIR spectroscopy, X-Ray diffraction, atomic absorption spectroscopy, UV-Visible spectroscopy, and dynamic light scattering measurements were employed to characterize the multifunctional system at different stages of engineering. The ratio of relaxivities r2/r1 is 4.6 at 1.5 T for the MNP prepared with 0.5 molar ratio of Mn/Fe based on MR images obtained from phantom and tumor bearing mouse. The value of r2/r1 shows that the 0.5 molar ratio of Mn/Fe can be used to prepare MNP for the production of dual mode contrast in MR imaging.
