Relaxivity R1 Research Articles

Iron–polyphenol dendritic complexes for regulating amplification of phenolic hydroxyl groups to improve magnetic resonance imaging

Iron-based polyphenol complexes have been widely used as T1 contrast agents in tumor diagnosis. However, due to the irregularity of natural polyphenol ligand structures, it is challenging to determine the influence that the structures of ligands have on their T1 contrast properties. Herein, based on dendrimers, a series of polyphenol compounds (P1, P2, and P3) with simple and ordered structures were coordinated with iron (III) (Fe3+) to explore the effect that the structures of the polyphenols have on their T1 contrast performance. The new Fe3+-based polyphenol complexes based on the P1, P2, and P3 ligands with regular amplification of their phenolic hydroxyl groups exhibit increased longitudinal relaxivity (r1), due to the effective proton exchange generated by the hydrogen-bonding network between the phenolic hydroxyl groups and bound water. Moreover, the designed Fe3+-based polyphenol complexes exhibit good T1 contrast effect both in vitro and in vivo. Based on this, the relaxivity properties of Fe3+-based contrast agents may be improved by modifying their coordination structure, which could further facilitate the development of Fe3+-based complexes that exhibit excellent magnetic resonance imaging effect for disease diagnosis.

MR-oximetry with fat DESPOT

PurposeThe R1 relaxation rate of fat is a promising marker of tissue oxygenation. Existing techniques to map fat R1 in MR-oximetry offer limited spatial coverage, require long scan times, or pulse sequences that are not readily available on clinical scanners. This work addresses these limitations with a 3D voxel-wise fat R1 mapping technique for MR-oximetry based on a variable flip angle (VFA) approach at 3 T. MethodsVarying levels of dissolved oxygen (O2) were generated in a phantom consisting of vials of safflower oil emulsion, used to approximate human fat. Joint voxel-wise mapping of fat and water R1 was performed with a two-compartment VFA model fitted to multi-echo gradient-echo magnitude data acquired at four flip angles, referred to as Fat DESPOT. Global R1 was also calculated. Variations of fat, water, and global R1 were investigated as a function of the partial pressure of O2 (pO2). Inversion-prepared stimulated echo magnetic resonance spectroscopy was used as the reference technique for R1 measurements. ResultsFat R1 from Fat DESPOT was more sensitive than water R1 and global R1 to variations in pO2, consistent with previous studies performed with different R1 mapping techniques. Fat R1 sensitivity to pO2 variations with Fat DESPOT (median O2 relaxivity r1, O2 = 1.57× 10−3 s−1 mmHg−1) was comparable to spectroscopy-based measurements for methylene, the main fat resonance (median r1, O2= 1.80 × 10−3 s−1 mmHg−1). ConclusionFat and water R1 can be measured on a voxel-wise basis using a two-component fit to multi-echo 3D VFA magnitude data in a clinically acceptable scan time. Fat and water R1 measured with Fat DESPOT were sensitive to variations in pO2. These observations suggest an approach to 3D in vivo MR oximetry.

Multifunctional tunable ZnFe2O4@MnFe2O4 nanoparticles for dual-mode MRI and combined magnetic hyperthermia with radiotherapy treatment.

With the increase in non-communicable diseases, cancer is becoming one of the most lethal ailments of the coming decades. Significant progress has been made in the development of NPs that combine diagnostic and therapeutic properties in a single system. Multimodal NPs that sequentially perform MRI diagnostics with increased contrast and then act as synergistic agents for magnetic hyperthermia and radiotherapy can be considered as next-generation anticancer drugs. Thus, we propose a systematic study of composite theranostic ZnFe2O4@MnFe2O4 NPs for the first time. Two types of magnetic NPs with MnFe2O4 shell thicknesses of 0.5 (ZM0.5) and 1.7 nm (ZM3) were prepared via hydrothermal synthesis. Tuning the shell thickness was shown to influence the NP r2 and r1 relaxivities and allow T1-T2 dual-mode contrast agents to be obtained. A radiotherapy study demonstrated a significant dose factor enhancement (about 40%) for both NP types. The specific absorption rate of ZM3 in a 100 Oe alternating magnetic field with a frequency of 75 kHz was found to be 8 W g-1, which results in heating up to 42 °C within a few seconds. This work presents high-performance multifunctional NPs capable of combining different diagnostic and therapeutic methods for a full course of treatment using only one type of NP.

Tumor microenvironment responsive T1-T2 dual-mode contrast agent Fe3O4@ZIF-8-Zn-Mn NPs for in vivo magnetic resonance imaging.

Activated T1-T2 contrast agents can effectively improve the sensitivity and diagnosis accuracy of magnetic resonance imaging (MRI), but the construction of such contrast agents still remains a great challenge. In this work, a pH- and glutathione (GSH)-responsive T1-T2 dual-mode contrast agent, Fe3O4@ZIF-8-Zn-Mn nanoparticles (NPs), with simple components was constructed via simply assembly of paramagnetic Mn2+ ions (as T1 contrast agent) and Fe3O4 NPs (as T2 contrast agent) into a pH- and GSH-sensitive Zn-zeolitic imidazole framework (ZIF-8) matrix. Under neutral conditions, Fe3O4@ZIF-8-Zn-Mn NPs show good stability and weak T1-T2 dual-mode MRI contrast effect (r1 = 0.82 mM-1 s-1, r2 = 21.28 mM-1 s-1) due to the magnetic interference between Fe3O4 NPs and paramagnetic Mn2+ ions. In contrast, under acidic environment (pH = 6.5-5.5) and in the present GSH (0-4 mM), Fe3O4@ZIF-8-Zn-Mn NPs can be disassembled and release Fe3O4 NPs and paramagnetic Mn2+ ions, which causes simultaneous recovery of T1 and T2 imaging performances with enhanced r1 and r2 relaxation values up to 6.9 and 9.9 times, respectively. Moreover, in vivo MRI experiments showed that after the intravenous injection of Fe3O4@ZIF-8-Zn-Mn NPs for about one hour, the T1-weighted imaging of the tumor site becomes brighter with T1 signal enhanced by about 31%, while the T2-weighted imaging of the tumor site becomes darker with T2 signal enhanced by nearly 30%, suggesting the great potential of Fe3O4@ZIF-8-Zn-Mn NPs to be used as a tumor microenvironment-responsive T1-T2 dual-mode contrast agent for sensitive tumor imaging.

Curcumin Coated Ultra-Small Iron Oxide Nanoparticles as T1 Contrast Agents for Magnetic Resonance Imaging of Cancer Cells.

The application of nanotechnology in the molecular diagnosis and treatment of cancer is essential. This study aimed to investigate the influence of curcumin-coated ultra-small superparamagnetic iron oxide (USPIO) as a T1 contrast agent in Magnetic Resonance Imaging (MRI). In this experimental study, the influence of curcumin-coated USPIO (Fe3O4@C) on the diagnosis of the cancer cell line was investigated. After synthesis, characterization, and relaxation of Fe3O4@C, the contrast changes in T1-weight MRI to mouse colon carcinoma 26 cell line were evaluated in vitro. Fe3O4@C nanoparticles (NPs) are good at imaging; based on a relaxometry test, the r1 and r2 relaxivities of Dotarem were 3.139 and 0.603 mM-1s-1, respectively. Additionally, the r1 and r2 relaxivities of Fe3O4@C were 3.792 and 1.3 mM-1s-1, respectively, with the rate of 2.155 of r2/r1 NPs. The NPs can be identified as a positive contrast agent with a weight of T1 in MRI. The coresh-ell Fe3O4@C NPs can be effective in cancer treatment and diagnosis because of the therapeutic effects of curcumin and the properties of USPIO.

NMR Methods to Study the Dynamics of SH2 Domain-Phosphopeptide Complexes.

Nuclear magnetic resonance (NMR) spectroscopy is the method of choice for studying the dynamics of biological macromolecules in solution. By exploiting the intricate interplay between the effects of protein motion (both overall rotational diffusion and internal mobility) and nuclear spin relaxation, NMR allows molecular motion to be probed at atomic resolution over a wide range of timescales, including picosecond (bond vibrations and methyl-group rotations), nanosecond (loop motions and rotational diffusion), and microsecond-millisecond (ligand binding, allostery). In this chapter, we describe different NMR pulse schemes (R1, R1ρ, heteronuclear NOE, and CPMG relaxation dispersion) to characterize the dynamics of SH2 domains. As an example, we use the N-SH2 domain of protein tyrosine phosphatase SHP2 in complex with two phosphopeptides derived from immune checkpoint receptor PD-1 (ITIM and ITSM).

ATP-responsive Mn(II)-based T1 contrast agent for MRI.

A novel diacetylpyridylcarbohydrazide-DAPyCOHz-based manganese(II) chelate with dipicolylamine/zinc(II) (DPA/Zn2+) arms (MnLDPA-Zn2) was developed for adenosine triphosphate (ATP) responsive magnetic resonance imaging (MRI) T1 contrast applications. Compound 2 shows enhanced relaxivity (r1 = 11.52 mM-1 s-1) upon selective ATP binding over other phosphates.

A trade-off between ligand coating and crystallinity of Gd-doped ultrasmall CeO2 for improving relaxivity.

A Gd-doped ultrasmall CeO2 contrast agent was prepared with high longitudinal relaxivity (r1 = 10.1 mM-1 s-1, 7.0 T) through rationally regulating the crystallinity and surface coatings, providing a new paradigm for optimizing MRI performance. Moreover, responsive photoacoustic imaging (PAI) was established via tumor microenvironment-triggered oxidation, affording dual-modal imaging.

Ultra-small manganese dioxide nanoparticles with high T1 relaxivity for magnetic resonance angiography.

Gadolinium (Gd)-based contrast agents (CAs) for clinical magnetic resonance imaging are facing the problems of low longitudinal relaxivity (r1) and toxicity caused by gadolinium deposition. Manganese-based small molecule complexes and manganese oxide nanoparticles (MONs) are considered as potential alternatives to Gd-based CAs due to their better biocompatibility, but their relatively low r1 values and complicated synthesis routes slow down their clinical translation. Herein, we presented a facile one-step co-precipitation method to prepare MONs using poly(acrylic acid) (PAA) as a coating agent (MnO2/PAA NPs), which exhibited good biocompatibility and high r1 values. A series of MnO2/PAA NPs with different particle sizes were prepared and the relationship between the particle size and r1 was studied, revealing that the MnO2/PAA NPs with a particle size of 4.9 nm exhibited higher r1. The finally obtained MnO2/PAA NPs had a high r1 value (29.0 Mn mM-1 s-1) and a low r2/r1 ratio (1.8) at 1.5 T, resulting in a strong T1 contrast enhancement. In vivo magnetic resonance angiography with Sprague-Dawley (SD) rats further proved that the MnO2/PAA NPs showed better angiographic performance at low-dosage administration than commercial Gadovist® (Gd-DO3A-Butrol). Moreover, the MnO2/PAA NPs could be rapidly cleared out after imaging, which effectively minimized the toxic side effects. The MnO2/PAA NPs are promising candidates for MR imaging of vascular diseases.

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.

Ultrasound-enhanced theranostics of orthotopic breast cancer through a multifunctional core-shell tecto dendrimer-based nanomedicine platform.

Design of multifunctional nanoplatforms combined with ultrasound-targeted microbubble destruction (UTMD) technology for enhanced tumor accumulation is feasible to solve the bottleneck of theranostics. Herein, we present the development of zwitterion-modified gadolinium (Gd)-chelated core-shell tecto dendrimers (CSTDs) as a nanomedicine platform (PCSTD-Gd) for enhanced magnetic resonance (MR) imaging-guided chemo-gene therapy of orthotopic breast cancer with the assistance of UTMD. In our design, CSTDs synthesized via supramolecular recognition of β-cyclodextrin and adamantane were covalently linked with tetraazacyclododecane tetraacetic acid-Gd(III) chelators, modified with 1,3-propane sultone to achieve good protein-resistance property, and used for co-delivery of an microRNA 21 inhibitor (miR 21i) and an anticancer drug doxorubicin (DOX). The overall design is quite advantageous and cooperative. The CSTDs with a greater size than single-generation core dendrimers have amplified the enhanced permeability and retention effect for better passive tumor targeting, with a larger r1 relaxivity for sensitive MR imaging and serum-enhanced gene delivery efficiency due to the better compaction ability as well as the protein resistance ability, and with larger interior space for improved drug loading. Through the unique design and the assistance of UTMD, the obtained PCSTD-Gd/DOX/miR 21i polyplexes enable enhanced MR imaging-guided combined chemo-gene therapy of an orthotopic breast cancer model in vivo.

Slice & Dice: nested spin-lattice relaxation measurements.

Spin-lattice relaxation rate (R1) measurements are commonly used to characterize protein dynamics. However, the time needed to collect the data can be quite long due to long relaxation times of the low-gamma nuclei, especially in the solid state. We present a method to collect backbone heavy atom relaxation data by nesting the collection of datasets in the solid state. This method results in a factor of 2 to 2.5 times faster data acquisition for backbone R1 relaxation data for the 13C and 15N sites of proteins.

Biomolecular interactions studied by low-field NMR using SABRE hyperpolarization.

We demonstrate that low-field nuclear magnetic resonance provides a means for measuring biomacromolecular interactions without requiring a superconducting, or even a permanent magnet. A small molecule, 5-fluoropyridine-3-carboximidamide, is designed to be a specific ligand for the trypsin protein, while containing a fluorine atom as a nuclear spin hyperpolarizable label. With hyperpolarization by the parahydrogen based signal amplification by the reversible exchange method, fluorine NMR signals are detectable in the measurement field of 0.85 mT of an electromagnet, at a concentration of less than 100 μM. As a weak ligand for the protein, the hyperpolarized molecule can serve as a reporter for measuring the binding of other ligands of interest, illustrated by the determination of the dissociation constant KD of benzamidine from changes in the observed R2 relaxation rates. A signal enhancement of more than 106 compared to Boltzmann polarization at the measurement field indicates that this experiment is not feasible without prepolarization. The extended magnetic field range for the measurement of biomolecular interactions under near physiological conditions, with a protein concentration on the order of 10 μM or less, provides a new option for screening of ligand binding, measurement of protein-protein interactions, and measurement of molecular dynamics.

Controlling Disassembly of Paramagnetic Prodrug and Photosensitizer Nanoassemblies for On-Demand Orthotopic Glioma Theranostics

Controlling delivery and release of therapeutic agents to accomplish on-demand synergistic therapy of orthotopic gliomas is desired but challenging. Here, we report a glioma targeting and redox activatable theranostic nanoprobe (Co-NP-RGD1/1) for magnetic resonance (MR) and fluorescence (FL) bimodal imaging-guided on-demand synergistic chemotherapy/photodynamic therapy (Chemo-PDT) of orthotopic gliomas. Co-NP-RGD1/1 is formed via molecular coassembly of two paramagnetic and fluorogenic small-molecule probes CPT-RGD and PPa-RGD at an optimized molar ratio of 1/1, which shows a high longitudinal relaxivity (r1 = 17.0 ± 0.6 mM-1 s-1, 0.5 T) but weak FL emissions and low Chemo-PDT activity. Upon reduction by endogenous glutathione (GSH), Co-NP-RGD1/1 disassemble and release small molecules 2-RGD, chemodrug camptothecin (CPT), and near-infrared (NIR) photosensitizer (PS) PPa-SH that further binds to endogenous albumin to form PPa-SH-albumin complex, allowing to turn on FL, chemotherapeutic efficacy, and PDT activity for synergistic Chemo-PDT of orthotopic U87MG or U251 gliomas in living mice. Moreover, Co-NP-RGD1/1 can also allow noninvasive detection and monitoring of orthotopic brain tumor growth via FL and MR imaging. Findings suggest the potential of cascade coassembly and stimuli-controlled intracellular disassembly strategy for constructing targeted and activatable nanoagents for improving combinational cancer theranostics.

Engineering sialic acid-coated mesoporous polydopamine nanomaterials for MRI-guided photothermal-enhanced synergistic effect chemodynamic lung cancer therapy

The mortality and morbidity rates of lung cancer are extremely high. Thus, the development of efficient diagnostic and therapeutic agents for lung cancer is warranted. We aimed to construct a new theranostic drug based on mesoporous polydopamine (MP) for dual T1/T2 magnetic resonance imaging (MRI)-guided chemo-photothermal chemotherapy. MP-nanomaterials (MP-NMs) loaded with superparamagnetic iron oxide nanomaterials (MP@SPIONs) were co-loaded with sialic acid (SA) and Fe3+ (SA-MP@SPION/Fe3+). Subsequently, SA-MP@SPION/Fe3+/CTX was engineered for tumor theranostics using a cabazitaxel (CTX)-loaded prodrug. MTT analysis revealed that PEG-SA-MP@SPION/Fe3+/CTX was water soluble and biocompatible. Further, the new theranostic agent was demonstrated to have a great photothermal conversion/stability, with relaxivity of r1 = 4.31 mM−1s−1 and r2 = 104.64 mM−1s−1, respectively, based on its in vitro photothermal and relaxivity ability. SA-MP@SPION/Fe3+/CTX efficiently encapsulated CTX, enabling both pH- and thermally-induced drug release. Notably, SA-MP@SPION/Fe3+/CTX was found to efficiently target lung cancer cells in vitro. Moreover, SA-MP@SPION/Fe3+/CTX exhibited more accurate dual-mode T1-T2 contrast imaging, unlike those that did not undergo SA alteration, and exerted a more significant therapeutic efficacy owing to its dynamic targeting capabilities and the combination of chemotherapy and photothermal treatment based on SA-MP@SPION/Fe3+/CTX NMs. According to our findings, the targeted nanoplatform, SA-MP@SPION/Fe3+/CTX, is an excellent tumor theranostic tool that could be effectively applied for lung cancer treatment.

Positive association of Cerebral Amyloid Angiopathy (CAA) with R2 Relaxation rate: A study of ex‐vivo MRI and pathology

AbstractBackgroundCerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid‐β in the walls of cortical and leptomeningeal small vessels. CAA is common in older adults and has been associated with cognitive decline and dementia. In this work, the association of CAA with the transverse relaxation rate R2 values in a large community‐based cohort of older adults was investigated.MethodCerebral hemispheres from 797 participants of three cohort studies of aging, the Rush Memory and Aging Project, the Minority Aging Research Study, and the Religious Orders Study (Figure 1) were included in this work. All hemispheres were imaged ex‐vivo at approximately 30 days postmortem using 3T clinical MRI scanners. Each scan included a multi‐echo spin‐echo sequence, and in each voxel, the signals from the different echoes were used to fit a mono‐exponential T2 decay equation (R2 is the reciprocal of T2). The resulting R2 maps were registered to an ex‐vivo brain hemisphere template using ANTS. Following the MRI scan, each hemisphere underwent thorough neuropathologic evaluation (Figure 2). The assessed pathologies were: CAA, Alzheimer’s pathology, LATE‐NC, hippocampal sclerosis (HS), Lewy bodies, arteriolosclerosis, atherosclerosis, gross and microscopic infarcts.Voxel‐wise linear regression was conducted to test the association of R2 with CAA, controlling for all other neuropathologies listed above, demographics (age at death, sex, education), and other variables (postmortem interval to immersion in fixative, postmortem interval to ex‐vivo MRI, scanners). Statistical analysis was done using PALM with tail‐accelerated 1000 permutations, threshold‐free cluster enhancement, and family‐wise error rate correction. Statistical significance was set at p<0.05.ResultThe voxel‐wise analysis revealed a spatial pattern of higher R2 values for higher CAA burden (Figure 3). The pattern included subcortical structures such as the caudate, putamen, nucleus accumbens, hippocampus, regions in the insula, anterior cingulate cortex, orbitofrontal cortex, and superior frontal cortex (Figure 3). No voxel showed a negative association between R2 values and CAA burden.ConclusionOur work showed that CAA is associated with higher R2 among older adults, independent of other neuropathologies and demographic factors. The spatial pattern for this association derived from the voxel‐wise analysis included subcortical and frontal lobe structures.

Synthesis and Characterization of Gold-Shell Magnetic Nanowires for Theranostic Applications

Increasing interest has been given in recent years to alternative physical therapies for cancer, with a special focus on magneto-mechanical actuation of magnetic nanoparticles. The reported findings underline the need for highly biocompatible nanostructures, along with suitable mechanical and magnetic properties for different configurations of alternating magnetic fields. Here, we show how the biocompatibility of magnetic nanowires (MNWs), especially CoFe, can be increased by gold coating, which can be used both in cancer therapy and magnetic resonance imaging (MRI). This study provides a new approach in the field of theranostic applications, demonstrating the capabilities of core–shell nanowires to be used both to increase the cancer detection limit (as T2 contrast agents) and for its treatment (through magneto-mechanical actuation). The MNWs were electrodeposited in alumina templates, whereas the gold layer was electroless-plated by galvanic replacement. The gold-coated CoFe nanowires were biocompatible until they induced high cellular death to human osteosarcoma cells via magneto-mechanical actuation. These same MNWs displayed increased relaxivities (r1, r2). Our results show that the gold-coated CoFe nanowires turned out to be highly efficient in tumor cell destruction, and, at the same time, suitable for MRI applications.

Transient On- and Off-Pathway Protein Folding Intermediate States Characterized with NMR Relaxation Dispersion.

The earliest events in the folding of a protein are in general poorly understood. We used NMR R2 relaxation dispersion experiments to study transient local collapse events in the unfolded-state (U) conformational ensemble of apomyoglobin (apoMb). Local residual secondary structure (seen in regions corresponding to the A, D, E, and H helices of the folded protein) is largely unchanged over the pH range of 2.3-2.75, yet a significant pH-dependent increase in the conformational exchange contribution to the R2 relaxation rate (Rex) indicates that transient intramolecular contacts occur on a microsecond to millisecond time scale at pH 2.75. A comparison of 15N and 13CO relaxation dispersion data at pH 2.75 for residues in the A, B, G, and H regions, which participate in the earliest folding intermediates, indicates that chain collapse and secondary structure formation are rapid and concomitant. Increasingly stabilizing conditions (lower temperature, higher pH) result in the observation of a relaxation dispersion in the C, CD, and E regions of the protein, which are known to fold at later stages. Mutation of Trp14 in the A-helix region to Ala eliminates conformational exchange throughout the protein, and the mutation of hydrophobic residues in other regions results in the selective inhibition of conformational exchange in the B, G, or H regions. The R2 dispersion data for WT apoMb at pH 2.75 and 10 °C are best fit to a four-state model ABGH ⇆ AGH ⇆ U ⇆ ABCD that includes on-pathway (AGH and ABGH) and off-pathway (ABCD) transiently folded states, both of which are required to explain the behavior of the mutant proteins. The off-pathway intermediate is destabilized at higher temperatures. Our analysis provides insights into the earliest stages of apoMb folding where the collapsing polypeptide chain samples both productive and nonproductive states with stabilized secondary structure.

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.

Magnetic properties, phase evolution, hollow structure and biomedical application of hematite (α-Fe2O3) and QUAIPH

We investigate synthesis, phase evolution, hollow and porous structure and magnetic properties of quasi-amorphous intermediate phase (QUAIPH) and hematite (α-Fe2O3) nanostructure synthesized by annealing of akaganeite (β-FeOOH) nanorods. It is found that the annealing temperature determines the phase composition of the products, the crystal structure/size dictates the magnetic properties whereas the final nanorod morphology is determined by the starting material. Annealing of β-FeOOH at ∼300 °C resulted in the formation of hollow QUAIPH nanorods. The synthesized material shows low-cytotoxicity, superparamagnetism and good transverse relaxivity, which is rarely reported for QUAIPH. The QUAIPH nanorods started to transform to porous hematite nanostructures at ∼350 °C and phase transformation was completed at 600 °C. During the annealing, the crystal structure changed from monoclinic (akaganeite) to quasi-amorphous and rhombohedral (hematite). Unusually, the crystallite size first decreased (akaganeite → QUAIPH) and then increased (QUAIPH → hematite) during annealing whereas the nanorods retained particle shape. The magnetic properties of the samples changed from antiferromagnetic (akaganeite) to superparamagnetic with blocking temperature TB = 84 K (QUAIPH) and finally to weak-ferromagnetic with the Morin transition at TM = 244 K and high coercivity HC = 1652 Oe (hematite). The low-cytotoxicity and MRI relaxivity (r2 = 5.80 mM−1 s−1 (akaganeite), r2 = 4.31 mM−1 s−1 (QUAIPH) and r2 = 5.17 mM−1 s−1 (hematite)) reveal potential for biomedical applications.