Relaxivity Values Research Articles

Modification of the SDR equation for permeability prediction

We evaluate the potential of permeability prediction of the original and modified versions of the Schlumberger-Doll Research (SDR) equation that is applied to data of nuclear magnetic resonance (NMR) relaxometry. Different definitions of characteristic relaxation time are considered. In a further modification, pore radius replaces the characteristic relaxation time in the original SDR equation. Only a good estimate of the surface relaxivity enables a reliable transformation from the relaxation time distribution (RTD) into the pore radius distribution (PRD). A recently published approach considers the specific surface area per unit pore volume (Spor) and the weighted harmonic mean (T2hm) of the RTD for the determination of an individual value of surface relaxivity for each sample. The evaluation is performed for three sample sets originating from different sandstone formations. The good predictive quality of the original SDR equation is confirmed. However, the prefactors have to be adjusted by calibrating with core data. We demonstrate that the use of average pore radii instead of average relaxation times enables a better permeability prediction. The weighted harmonic mean of the PRD, which proves to be a reliable proxy for the effective hydraulic radius, provides a high quality permeability prediction.

CHARACTERISTIC OF PORE STRUCTURE AND FLOW PROPERTY IN SANDSTONES BASED ON LOW FIELD NUCLEAR MAGNETIC RESONANCE

Surface relaxivity is the most significant parameter that converts transverse relaxation time into pore size in porous media. However, the value of surface relaxivity is difficult to obtain. This paper focuses on measuring surface relaxivity to evaluate permeability of two types of sandstones (loose sandstone and tight sandstone), combining the high-speed centrifugation with nuclear magnetic resonance test. The results reveal the surface relaxivities for loose sandstones (1.89-2.20 μm/s) are larger than that for tight sandstones (0.69-0.87 μm/s). The measured surface relaxivity is consistent with that from the method of monolayer water adsorption. During centrifugation, the variation of water content is analyzed, including the pore with different size categories. Based on the measured surface relaxivity, the Schlumberger doll research model is used to estimate the absolute permeability of sandstones.

Углеродные наночастицы, легированные медью, как двух-модальный нанозонд для люминесцентной и магнитно-резонансной визуализации

In this work, copper-doped carbon nanoparticles with emission in a wide spectral range and the ability to change the relaxation times of water protons during magnetic resonance imaging were fabricated. A high relaxivity value r1 = 0.92 mM-1∙s-1 was achieved, which is the highest value of r1 for copper nanoparticles, to our knowledge. The suggested carbon nanoparticles are promising two-modal nanoprobes for bioimaging.

Mn(II) complex impregnated porous silica nanoparticles as Zn(II)-responsive "Smart" MRI contrast agent for pancreas imaging.

Type-1 and type-2 diabetes mellitus are metabolic disorders governed by the functional efficiency of pancreatic β-cells. The activities of the cells toward insulin production, storage, and secretion are accompanied by Zn(II) ions. Thus, for non-invasive pathology of the cell, developing Zn(II) ion-responsive MRI-contrast agents has earned considerable interest. In this report, we have synthesized a seven-coordinate, mono(aquated) Mn(II) complex (1), which is impregnated within a porous silica nanosphere of size 13.2 nm to engender the Mn(II)-based MRI contrast agent, complex 1@SiO2NP. The surface functionalization of the nanosphere by the Py2Pic organic moiety for the selective binding of Zn(II)-ions yields complex 1@SiO2-Py2PicNP, which exhibits r1 = 13.19 mM-1 s-1. The relaxivity value elevates to 20.38 mM-1 s-1 in the presence of 0.6 mM BSA protein at pH 7.4. Gratifyingly, r1 increases linearly with the increase of Zn(II) ion concentration and reaches 39.01 mM-1 s-1 in the presence of a 40 fold excess of the ions. Thus, Zn(II)-responsive contrast enhancement in vivo is envisaged by employing the nanoparticle. Indeed, a contrast enhancement in the pancreas is observed when complex 1@SiO2-Py2PicNP and a glucose stimulus are administered in fasted healthy C57BL/6 mice at 7 T.

An iron(III) complex-based supramolecular organic framework (SOF) as a theranostic platform via magnetic resonance imaging-guided chemotherapy.

It is crucially important to explore the additional metal-endowed functions of supramolecular organic frameworks (SOFs) for expanding their applications. In this work we have reported the performance of a SOF (designated as Fe(III)-SOF) as a theranostic platform via magnetic resonance imaging (MRI)-guided chemotherapy. The Fe(III)-SOF may be used as an MRI contrast agent for cancer diagnosis because the building unit (iron complex) contains high spin iron(III) ions. Additionally, the Fe(III)-SOF may also be used as a drug carrier because it possesses stable internal voids. We loaded doxorubicin (DOX) into the Fe(III)-SOF to obtain a DOX@Fe(III)-SOF. The Fe(III)-SOF showed good loading content (16.3%) and high loading efficiency (65.2%) for DOX. Additionally, the DOX@Fe(III)-SOF had a relatively modest relaxivity value (r2 = 19.745 mM-1 s-1) and exhibited the strongest negative contrast (darkest) at 12 h of post-injection. Furthermore, the DOX@Fe(III)-SOF effectively inhibited tumor growth and showed high anticancer efficiency. In addition, the Fe(III)-SOF was biocompatible and biosafe. Therefore, the Fe(III)-SOF was an excellent theranostic platform and may have potential applications in tumor diagnosis and treatment in the future. We believe that this work will initiate extensive research endeavors not only on the development of SOFs, but also on the construction of theranostic platforms based on SOFs.

Quercetin@Gd3+ doped Prussian blue nanocubes induce the pyroptotic death of MDA-MB-231 cells: combinational targeted multimodal therapy, dual modal MRI, intuitive modelling of r1-r2 relaxivities.

Quercetin (Qu), a potential bioflavonoid has gained considerable interest as a promising chemotherapeutic drug which can inhibit the proliferation of triple-negative breast cancer (TNBC) cells due to its regulation of the expression of tumor-suppressor gene metastasis and antioxidant property. Notably, Qu exhibits a very negligible cytotoxic effect on normal cells, even with high-dose treatment, while it is shows high affinity to TNBC. However, the efficiency of Qu is limited clinically due to its poor bioavailability, caused by its low aqueous solubility (2.15 μg mL-1 at 25 °C), rapid gastrointestinal digestion and chemical instability in alkaline and neutral media. Herein, polydopamine (PDA)-coated, NH2-PEG-NH2 and hyaluronic acid (HA)-functionalized Gd3+-doped Prussian blue nanocubes (GPBNC) are reported as a multifunctional platform for the codelivery of Qu as a chemotherapeutic agent and GPBNC as a photodynamic (PDT) and photothermal (PTT) agent with improved therapeutic efficiency to overcome theses barriers. PDA, NH2-PEG-NH2 and HA stabilize GPBNC@Qu and facilitate bioavailability and active-targeting, while absorption of near infrared (NIR) (808 nm; 1 W cm-2) induces PDT and PTT activities and dual T1-T2-weighted magnetic resonance imaging (MRI) with high relaxometric parameters (r1 10.06 mM-1 s-1 and r2 24.96 mM-1 s-1 at a magnetic field of 3 T). The designed platform shows a pH-responsive Qu release profile and NIR-induced therapeutic efficiency of ∼79% in 20 minutes of irradiation, wherein N-terminal gardermin D (N-GSDMD) and a P2X7-receptor-mediated pyroptosis pathway induces cell death, corroborating the up-regulation of NLRP3, caspase-1, caspase-5, N-GSDMD, IL-1β, cleaved Pannexin-1 and P2X7 proteins. More interestingly, the increasing relaxivity values of Prussian blue nanocubes with Gd3+ doping have been explained on the basis of Solomon-Bloembergen-Morgan theory, considering inner- and outer-sphere relaxivity, wherein crystal defects, coordinated water molecules, tumbling rate, metal to water proton distance, correlation time, magnetisation value etc. play a significant role. In summary, our study suggests that GPBNC could be a beneficial nanocarrier for theranostic purposes against TNBC, while our conceptual study clearly demonstrates the role of various factors in increasing relaxometric parameters.

Bipyridil-based chelators for Gd(III) complexation: kinetic, structural and relaxation properties.

In the last 20 years, research in the field of MRI (magnetic resonance imaging) contrast agents (CAs) has been intensified due to the emergence of a disease called nephrogenic systemic fibrosis (NSF). NSF has been linked to the in vivo dissociation of certain Gd(III)-based compounds applied in MRI as CAs. To prevent the dechelation of the probes after intravenous injection, the improvement of their in vivo stability is highly desired. The inertness of the Gd(III) chelates can be increased through the rigidification of the ligand structure. One of the potential ligands is (2,2',2'',2'''-(([2,2'-bipyridine]-6,6'-diylbis(methylene))bis(azanetriyl))tetraacetic acid) (H4DIPTA), which has been successfully used as a fluorescent probe for lanthanides; however, it has never been considered as a potential chelator for Gd(III) ions. In this paper, we report the thermodynamic, kinetic and structural features of the complex formed between Gd(III) and DIPTA. Since the solubility of the [Gd(DIPTA)]- chelate is very low under acidic conditions, hampering its thermodynamic characterization, we can only assume that its stability is close to that determined for the structural analogue [Gd(FENTA)]- (H4FENTA: (1,10-phenanthroline-2,9-diyl)bis(methyliminodiacetic acid)), which is similar to that determined for the agent [Gd(DTPA)]2- routinely used in clinical practice. Unfortunately, the inertness of [Gd(DIPTA)]- is significantly lower (t1/2 = 1.34 h) than that observed for [Gd(EGTA)]- and [Gd(DTPA)]2- as a result of its spontaneous dissociation pathway during dechelation. The relaxivity values of [Gd(DIPTA)]- are comparable with those of [Gd(FENTA)]- and somewhat higher than the values characterizing [Gd(DTPA)]2-. Luminescence lifetime measurements indicate the presence of one water molecule (q = 1) in the inner sphere of the complex with a relatively high water exchange rate (k298ex = 43(5) × 106 s-1). DFT calculations suggest a rigid distorted tricapped trigonal prismatic polyhedron for the Gd(III) complex. On the basis of these results, we can conclude that the bipyridine backbone is not favourable with respect to the inertness of the chelate.

Liposomal MRI probes containing encapsulated or amphiphilic Fe(III) coordination complexes.

Liposomes containing high-spin Fe(III) coordination complexes were prepared towards the production of T1 MRI probes with improved relaxivity. The amphiphilic Fe(III) complexes were anchored into the liposome with two alkyl chains to give a coordination sphere containing mixed amide and hydroxypropyl pendant groups. The encapsulated complex contains a macrocyclic ligand with three phosphonate pendants, [Fe(NOTP)]3-, which was chosen for its good aqueous solubility. Four types of MRI probes were prepared including those with intraliposomal Fe(III) complex (LipoA) alone, amphiphilic Fe(III) complex (LipoB), both intraliposomal and amphiphilic complex (LipoC) or micelles formed with amphiphilic complex. Water proton relaxivities r1 and r2 were measured and compared to a small molecule macrocyclic Fe(III) complex containing similar donor groups. Micelles of the amphiphilic Fe(III) complex had proton relaxivity values (r1 = 2.6 mM-1 s-1) that were four times higher than the small hydrophilic analog. Liposomes with amphiphilic Fe(III) complex (LipoB) have a per iron relaxivity of 2.6 mM-1 s-1 at pH 7.2, 34 °C at 1.4 T whereas liposomes containing both amphiphilic and intraliposomal Fe(III) complexes (lipoC) have r1 of 0.58 mM-1 s-1 on a per iron basis consistent with quenching of the interior Fe(III) complex relaxivity. Liposomes containing only encapsulated [Fe(NOTP)]3- have a lowered r1 of 0.65 mM-1 s-1 per iron complex. Studies show that the biodistribution and clearance of the different types liposomal nanoparticles differ greatly. LipoB is a blood pool agent with a long circulation time whereas lipoC is cleared more rapidly through both renal and hepatobiliary pathways. These clearance differences are consistent with lower stability of LipoC compared to LipoB.

Peptide-Based Hydrogels and Nanogels Containing Gd(III) Complexes as T1 Relaxation Agents.

New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2-), [Gd(DTPA)]2-, and ([Gd(AAZTA)]-) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino acids (differently ordered Gly, Ala, Val, Leu and Ile) and a charged lysine at the amidated C-terminal were used for the formation of the hydrogels. Particular attention was paid to the investigation of the morphological and rheological properties of the nanoparticles, in addition to the assessment of the ability (relaxivity) of the confined complexes to accelerate the longitudinal relaxation rate of the water protons localized in the polymeric network. The relaxivity values at high magnetic fields (>0.5 T) of the paramagnetic hydrogels appear to be more than five times higher than those of isolated chelates in an aqueous solution, reaching a value of 25 mmol-1 s-1 for Fmoc-K2+[Gd(BOPTA)]2- at 0.5 T and 310 K. Furthermore, an interesting trend of decrease of relaxivity with increasing the degree of rigidity of the hydrogel was observed. The type of interactions between the various complexes and the polymeric network also plays a key role in influencing the relaxivity values of the final materials. Nanogels were also obtained from the submicronization of the hydrogel containing [Gd(BOPTA)]2- chelate. Circular dichroism, dynamic light scattering and relaxometric investigations on these nanoparticles revealed the formation of nanogels endowed with higher relaxivities (r1 = 41 mM-1 s-1 at 0.5 T MHz and 310 K) than the corresponding hydrogels.

Engineered Protein-Driven Synthesis of Tunable Iron Oxide Nanoparticles as T1 and T2 Magnetic Resonance Imaging Contrast Agents.

Iron oxide nanoparticles (IONPs) have become one of the most promising nanomaterials for biomedical applications because of their biocompatibility and physicochemical properties. This study demonstrates the use of protein engineering as a novel approach to design scaffolds for the tunable synthesis of ultrasmall IONPs. Rationally designed proteins, containing different number of metal-coordination sites, were evaluated to control the size and the physicochemical and magnetic properties of a set of protein-stabilized IONPs (Prot-IONPs). Prot-IONPs, synthesized through an optimized coprecipitation approach, presented good T1 and T2 relaxivity values, stability, and biocompatibility, showing potential for magnetic resonance imaging (MRI) applications.

Ultrasmall Fe3O4 and Gd2O3 hybrid nanoparticles for T1-weighted MR imaging of cancer

AbstractGadolinium-based contrast agents (GdCAs) have been the most frequently used T1-weighted magnetic resonance imaging (MRI) contrast agents for decades. However, they have serious disadvantages such as low longitudinal relaxivity value (r1) and high dose associated-nephrotoxicity that restrict their wide applications. These emphasize the need for an ideal stable and biocompatible T1-weighted CA with high contrast enhancement performance. Here, we propose a wet-chemical synthesis technique to form a nanocomposite consisting of ultrasmall iron oxide nanoparticles (US-IO) and Gd2O3 hybrid nanoparticles stabilized with dextran (FG-HNPs) for T1-weighted MR imaging. Relaxometry study showed that FG-HNPs have a high r1 value (42.28 mM−1S−1) and low relaxivity ratio (r2/r1: 1.416) at 3.0T. In vivo MRI contrast enhancement factor (ΔSNR) for FG-HNPs (257.025 ± 17.4%) was found to be 1.99-fold higher than US-IO (129.102 ± 15%) and 3.35-fold higher than Dotarem (76.71 ± 14.2%) as routinely used T1-weighted CA. The cytotoxicity assay and histological examination confirmed the biocompatibility of FG-HNPs. The biodistribution study, transmission electron microscopy (TEM) and Prussian blue (PB) staining of tumor tissue proved the effective tumor localization of FG-HNPs. Therefore, FG-HNPs can be suggested as a promising CA for T1-weighted MRI of tumors by virtue of their remarkable relaxivities and high biocompatibility.

Finite Element Simulation of NMR spectra and spin-spin relaxation of confined fluids under intense magnetic field gradients

Magnetic field gradients, generated as the magnetic response of solids and liquids to an applied field, directly affect the lineshapes and spin-spin relaxation time (T2) in Nuclear Magnetic Resonance (NMR) experiments and, therefore, the interpretation of fluid content in porous rocks. This paper presents a numerical study of pulse NMR spectra and T2 relaxation of fluids under realistic magnetic field gradients using the software COMSOL. Two physics sections are coupled: first, the internal magnetic field gradient is calculated in the whole system, comprising the solid matrix and a fluid mixture of brine and oil inside. Then, in the second, the NMR signal of the liquids, the Free Induction Decay (FID), is obtained by solving the Bloch–Torrey–MacConnell equations over the pore volume. The calculation of the NMR spectrum follows from the FID Fourier Transform (FFT). For the T2 calculations, a CPMG sequence is built by concatenating different studies. The obtained T2 reproduces the bulk value of the relaxation time, the dependence on the pore radii, and the relaxivity value correctly. Different magnetic properties, coupling parameters, pore sizes, and geometries are considered.

ROS-responsive chlorin e6 and silk fibroin loaded ultrathin magnetic hydroxyapatite nanorods for T1-magnetic resonance imaging guided photodynamic therapy in vitro

Magnetite hydroxyapatite nanoparticles show notable multifunctional therapeutic features in nanomedicine. However, designing MHAp nanoparticles with optimum dimensions, good stability and biocompatibility for specific biomedical applications is still in its infancy. Herein, a facile approach was employed to prepare ROS-responsive chlorin e6 and silk fibroin-loaded ultrathin magnetic hydroxyapatite nanorods for T1-magnetic resonance imaging and photodynamic therapy. Specifically, the Fe3O4-HAp nanorods were synthesized by the hydrothermal method, and then Pluronic® F-127 was used to improve the aqueous dispersion, biocompatibility, and loading capacity. Moreover, silk fibroin protein was encapsulated by a tri-block copolymer with good loading efficiency. Finally, the theranostic nano-assembly MHNRs-SF-Ce6 was completed by the addition of Ce6. The prepared MHNRs demonstrated excellent biocompatibility, cellular uptake, and ROS generation ability in in vitro after 660 nm laser irradiation, leading to the apoptosis of 4T1 mouse breast cancer cells. Notably, the designed MHNRs exhibited excellent r1 relaxivity value and T1 magnetic resonance imaging in vitro due to their minimal width (2 nm) of nanorods. Therefore, the obtained MHNRs-SF-Ce6 self-assembled nanoparticles provide an effective strategy for cancer diagnosis and photodynamic therapy.

Novel Salinomycin-Based Paramagnetic Complexes-First Evaluation of Their Potential Theranostic Properties.

Novel salinomycin (Sal)-based theranostic probes comprising two different paramagnetic metal ions, gadolinium(III) (Gd(III)) or manganese(II) (Mn(II)), as signal emitting motifs for MRI were synthesized and characterized by elemental analysis, infrared spectral analysis (IR), electroparamagnetic resonance (EPR), thermogravimetry (TG) differential scanning calorimetry (DSC) and electrospray ionization mass spectrometry (ESI-MS). To overcome the water insolubility of the two Sal-complexes, they were loaded into empty bacterial ghosts (BGs) cells as transport devices. The potential of the free and BGs-loaded metal complexes as theranostics was evaluated by in vitro relaxivity measurements in a high-field MR scanner and in cell culture studies. Both the free Sal-complexes (Gd(III) salinomycinate (Sal-Gd(III) and Mn(II) salinomycinate (Sal-Mn(II)) and loaded into BGs demonstrated enhanced cytotoxic efficacy against three human tumor cell lines (A549, SW480, CH1/PA-1) relative to the free salinomycinic acid (Sal-H) and its sodium complex (Sal-Na) applied as controls with IC50 in a submicromolar concentration range. Moreover, Sal-H, Sal-Gd(III), and Sal-Mn(II) were able to induce perturbations in the cell cycle of treated colorectal and breast human cancer cell lines (SW480 and MCF-7, respectively). The relaxivity (r1) values of both complexes as well as of the loaded BGs, were higher or comparable to the relaxivity values of the clinically applied contrast agents gadopentetate dimeglumine and gadoteridol. This research is the first assessment that demonstrates the potential of Gd(III) and Mn(II) complexes of Sal as theranostic agents for MRI. Due to the remarkable selectivity and mode of action of Sal as part of the compounds, they could revolutionize cancer therapy and allow for early diagnosis and monitoring of therapeutic follow-up.

MRI of radiation chemistry: First images and investigation of potential mechanisms.

Paramagnetic species such as O2 and free radicals can enhance T1 and T2 relaxation times. If the change in relaxation time is sufficiently large, the contrast will be generated in magnetic resonance images. Since radiation is known to be capable of altering the concentration of O2 and free radicals during water radiolysis, it may be possible for radiation to induce MR signal change. We present the first reported instance of x-ray-induced MR signal changes in water phantoms and investigate potential paramagnetic relaxation enhancement mechanisms associated with radiation chemistry changes in oxygen and free radical concentrations. Images of water and 10 mM coumarin phantoms were acquired on a 0.35 T MR-linac before, during, and after a dose delivery of 80Gy using an inversion-recovery dual-echo sequence with water nullified. Radiation chemistry simulations of these conditions were performed to calculate changes in oxygen and free radical concentrations. Published relaxivity values were then applied to calculate the resulting T1 change, and analytical MR signal equations were used to calculate the associated signal change. Compared to pre-irradiation reference images, water phantom images taken during and after irradiation showed little to no change, while coumarin phantom images showed a small signal loss in the irradiated region with a contrast-to-noise ratio (CNR) of 1.0-2.5. Radiation chemistry simulations found oxygen depletion of -11µM in water and -31µM in coumarin, resulting in a T1 lengthening of 24ms and 68ms respectively, and a simulated CNR of 1.0 and 2.8 respectively. This change was consistent with observations in both direction and magnitude. Steady-state superoxide, hydroxyl, hydroperoxyl, and hydrogen radical concentrations were found to contribute less than 1ms of T1 change. Observed radiation-induced MR signal changes were dominated by an oxygen depletion mechanism. Free radicals were concluded to play a minor secondary role under steady-state conditions. Future applications may include in vivo FLASH treatment verification but would require an MR sequence with a better signal-to-noise ratio and higher temporal resolution than the one used in this study.

Gadolinium-doped fluorescent carbon quantum dots as MRI contrast agents and fluorescent probes

In this research passivated gadolinium-doped carbon quantum dots (Gd-doped CQDs) were synthesized from starch by a hydrothermal method. The X-ray diffraction (XRD) pattern of the Gd-doped CQDs showed the formation of highly amorphous carbon. The Fourier transform infrared spectroscopy (FTIR) results suggested that the CQDs are functionalized with C-N and N–H bonds. The synthesized CQDs with a size distribution of 2–8 nm have an absorption peak at 271 nm in UV–Visible spectroscopy (UV–Vis). The photoluminescence (PL) in CQDs was dependent on the excitation wavelength. The QY of the synthesized CQDs was calculated to be 13.2%. The Gd-doped CQDs exhibited sustained PL in ionic solutions with different ionic strengths and different temperatures up to 65 °C. Fluorescence imaging on mouse C34/connective tissue-L929 cells confirmed that Gd-doped CQDs could be well distributed over the cytoplasm. The magnetic resonance imaging (MRI) showed that the Gd-doped CQDs have extremely high longitudinal and transverse relaxivity values of as high as 218.28 mM−1 s−1 and 364.68 mM−1 s−1. The synthesized Gd-doped CQDs are promising candidates as multifunctional imaging probes and MRI contrast agents in biomedical diagnosis and brain mapping applications.

Heparin-Superparamagnetic Iron Oxide Nanoparticles for Theranostic Applications.

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping. Dopamine (DA) was covalently linked to BSA and LMWH by amide linkages via carbodiimide coupling. The following ligand exchange reaction between the DA-BSA/DA-LMWH and OA was conducted in a biphasic system composed of water and hexane, affording LMWH@SPIONs stabilized in water by polystyrene sulfonate (PSS). Their size and morphology were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The LMWH@SPIONs’ cytotoxicity was tested, showing marginal or no toxicity for samples prepared with PSS at concentrations of 50 µg/mL. Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents.

Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd3+/DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd3+/DOX had a high photothermal conversion efficiency of 33.4% and excellent T1−MRI performance with a longitudinal relaxivity (r1) value of 14.966 mM−1·s − 1. Moreover, the results suggested that FMPDA/Gd3+/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd3+/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd3+/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics

Characterization of meningiomas with synthetic imaging.

Synthetic magnetic resonance imaging (SyMRI) is a novel quantitative and qualitative technique that permits the reconstruction of multiple image contrasts and quantitative maps from a single scan, thereby providing quantitative information and reducing scan times. The purpose of this study is to characterize intracranial meningiomas using SyMRI. The study included 35 patients with meningiomas (6 males, 29 females; mean age 61±17 years; range 21-90 years). Using 3T MR scanners, SyMRI was performed in addition to conventional FSET2, FLAIR, DWI, T1, and T1 with gadolinium. SyMRI software was used to generate T1, T2, and PD quantitative maps. Osirix MD was used to measure quantitative values of T1, T2, and PD using a ROI. We analyzed 42 meningiomas, 8 of which were associated with edema, and 5 contained calcifications. Mean relaxivity values of meningiomas on synthetic T1, T2, and PD maps at 3T MRI were 1382.6±391.7ms, 95.6±36.5ms, and 89.1±9.7 pu, respectively. Signal intensities in terms of T1, T2, and PD did not differ significantly between meningiomas with and without edema (p=.994, p=.356, and p=.221, respectively), nor between meningiomas containing and not containing calcifications (p=.840, p=.710, and p=.455, respectively). Values of T1 and T2 measured in meningiomas and the normal-appearing white matter approximated reference values found in the literature with other quantitative methods. The presented method offers a novel approach to characterize meningiomas through their relaxation parameters measured with a SyMRI sequence.

Manganese-functionalized MXene theranostic nanoplatform for MRI-guided synergetic photothermal/chemodynamic therapy of cancer

Abstract Two-dimensional transition metal carbides and nitrides (MXenes) nanosheets with high photothermal conversion efficiency as well as photothermal stability can efficiently generate remarkable hyperthermia for photothermal therapy (PTT) of cancer. However, mono-MXenes cannot exhibit precise diagnosis and treatment to complete ablation of cancer cells in the PTT process. To overcome this dilemma, an “all-in-one” nanoplatform of titanium carbide (Ti3C2) MXene-based composite nanosheets is developed for magnetic resonance imaging (MRI)-guided multi-modal hyperthermia and chemodynamic tumor ablation, which was achieved by bonding of manganese ion on the surface of Ti3C2, and then was the functionalized nanosheets was modified by biocompatible PEG (Mn-Ti3C2@PEG). Due to magnetic and Fenton-like catalytic properties of Mn components, Mn-Ti3C2@PEG not only acted as the contrast agents for T1-weighted MRI (relaxivity value of 1.05 mM−1 s−1), but also converted cellular H2O2 into highly toxic hydroxyl radicals (·OH) mediated chemodynamic therapy (CDT). Moreover, Furthermore, Mn-Ti3C2@PEG can efficiently suppressed tumor-growth by PTT, due to the high photothermal conversion capability and photothermal stability. As a proof-of-concept model, the as-designed Mn-Ti3C2@PEG nanoplatform shows simultaneous MRI and dual-modal treatment for effective suppression of tumor with minimized side effects both in vitro and in vivo, indicating the great potential for clinical cancer theranostics.