Water-Nanomaterial Interaction to Escalate Twin-Mode Magnetic Resonance Imaging.

Molecular imaging has gained utmost importance in the recent past in early diagnosis of diseases. In comparison to other imaging modalities, magnetic resonance imaging (MRI) has proven to extend its abilities not only for its usage of non-ionizing radiation but also for the high spatial resolution in soft tissues. A major limitation faced by MRI is the sensitivity in detecting diseased conditions until a certain stage. At present, this limitation is overcome with the use of contrast agents that show potential in altering the T1 and T2 relaxation times of the hydrogen protons. This modulation to the relaxation times leads to better contrast differences based on the type of contrast agent and the pulse sequence being engaged for acquiring images. Water molecules, as the major contributor of hydrogen protons, are proven to interact with such contrast agents. Major drawbacks noted with the marketed MRI contrast agents are their toxicity and renal clearance. To conquer these issues, magnetic nanomaterials are being researched for their abilities to match the contrast enhancement offered by traditional agents reducing their drawbacks. Furthermore, comparative diagnosis with both T1 and T2 contrast at the same time has also interested investigators. To achieve this, twin mode T1 and T2 weighted contrast agents are developed utilizing the remarkable properties extended by magnetic nanoplatforms. As a step forward, multimodal imaging agents are also being engineered based on these magnetic nanoplatforms that will generate cross-verified diagnoses using multiple imaging modalities with a unique imaging agent. This review starts by introducing the basics of MRI with major focus on the typical interactions of water molecules with a variety of magnetic nanomaterials. The review also concentrates on the clinical needs and nanomaterials available for twin T1 and T2 contrast with a minor introduction to multimodal imaging agents. In conclusion, the advent of MRI with the advantages offered by magnetic nanomaterials is summarized, leading to insights for future developments.

Excitation Wavelength Independent Carbon-Decorated Ferrite Nanodots for Multimodal Diagnosis and Stimuli Responsive Therapy.

The combination of superparamagnetism and excitation independency have been packed into carbon-decorated ferrite nanodots (CDs@MNFs) for the introduction of a cost-effective and less-toxic multimodal contrast agent in fluorescence/MR imaging to replace conventional heavy metal containing Gd-DOTA. The label-free surface engineered ferrite nanodots are capable of generating twin T1 (longitudinal) and T2 (transverse) weighted magnetic resonance (MR) along with fluorescence emission. The calculated molar relaxivities and molar radiant efficiency obtained from in vitro and in vivo studies are the indication of its multimodal efficacy in medical imaging compared to the conventional contrast agents. The cellular internalization of nanodots was established by confocal microscopy and flow cytometric assay, whereas the hemolysis and cell viability assays support their appreciable toxicity. Furthermore, the surface chemistry due to the presence of -COOH was utilized to attach the anticancer agent, doxorubicin (-NH2) making it an external stimuli responsive drug delivery vehicle for the treatment of cancer. Given the ease of fabrication, negligible toxicity, and significant contrast enhancement with stimuli responsive drug release kinetics CDs@MNFs prove to be a potential, cost-effective multimodal imaging agent which could be used for theragnosis.

Label Free Ultrasmall Fluoromagnetic Ferrite-clusters for Targeted Cancer Imaging and Drug Delivery.

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.

Camouflaged Nanosilver with Excitation Wavelength Dependent High Quantum Yield for Targeted Theranostic.

The present study shows the thorough investigations on optical properties and hydrodynamic diameters of glutathione (GSH) stabilized nanosilver clusters (AgNC) at different stages of synthesis and engineering for the optimized absolute quantum yield to generate fluorescent images of Dalton Lymphoma Ascites (DLA) tumour bearing mice. The initial increment of quantum yield was wavelength dependent and finally it became 0.509 which was due to the camouflaging or entrapment of AgNC in macrophages membranes. The potentiality of macrophages membrane camouflaged silver nanoclusters (AgM) was reflected in the cell viability assay and confocal based live dead cell assay where the AgM has better cell killing effect compared to AgNC with reduced dosage and in vivo mice imaging generated the clear visualization at the tumour sites. Therefore, from the present study, it can be considered that the camouflaged nanosilver can be used for targeted theranostic applications.

Author Correction: Effect of Mesoporous Nano Water Reservoir on MR Relaxivity.

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Effect of Mesoporous Nano Water Reservoir on MR Relaxivity.

In the present work, an attempt was made to engineer a mesoporous silica coated magnetic nanoparticles (MNF@mSiO2) for twin mode contrast in magnetic resonance imaging (MRI) with reduced toxicity. Superparamagnetic manganese ferrite nanoparticles were synthesized with variable mesoporous silica shell thickness to control the water molecules interacting with metal oxide core. 178 nm was the optimum hydrodynamic diameter of mesoporous ferrite core-shell nanoparticles that showed maximum longitudinal relaxation time (T1) and transverse relaxation time (T2) in MRI due to the storage of water molecules in mesoporous silica coating. Besides the major role of mesoporous silica in controlling relaxivity, mesoporous silica shell also reduces the toxicity and enhances the bioavailability of superparamagnetic manganese ferrite nanoparticles. The in vitro toxicity assessment using HepG2 liver carcinoma cells shows that the mesoporous silica coating over ferrite nanoparticles could exert less toxicity compared to the uncoated particle.

Optimized Mn-doped iron oxide nanoparticles entrapped in dendrimer for dual contrasting role in MRI.

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.