T1-weighted Magnetic Resonance Imaging Contrast Agents Research Articles

Iron-poly(tannic acid) biomimetic nanoparticles for targeted magnetic resonance imaging and drug delivery

The artificial nanomaterials with surface modification are promising platform in targeted therapy, but the nanomaterials are easily tracked by the reticuloendothelial system (RES) before reaching the target sites. Here we report a biomimetic camouflage system, macrophage membrane (MM) coated iron-poly(tannic acid) nanoparticels (Fe-PTA NPs) for targeted drug delivery and magnetic resonance imaging (MRI). The MM inherits the surface protein profiles from macrophage (RAW 264.7 cells), which would escape from RES and target the homotypic cells. The anticancer drug doxorubicin (DOX) was loaded into MM-Fe-PTA NPs, and demonstrated pH-responsive release ability. In addition, the MM-Fe-PTA NPs can be used as T1-weighted MRI contrast agents for targeted MRI. This cell membrane camouflage strategy has great potential and challenge for clinic targeted therapy.

Multicomponent magnetic spinels: From complexity of crystal chemistry to coupled magnetic resonance imaging (MRI)

Spinels have a rich history that spans complexities of their structures to multitude of useful properties and intriguing phenomena. Herein, we demonstrate the versatility and elegance of ferrite-spinel based magnetic nanostructures (MNSs) as a contrast agent in magnetic resonance imaging (MRI). We show that the magnetic properties of the inverse spinel Fe3O4 MNS can be enhanced by tuning their crystal chemistry. After doping with Mn2+ and Zn2+ into Fe3O4 MNS at a right stoichiometry, high saturation magnetization and magnetic anisotropy were observed due to rearrangement and specific positions of Mn2+, Zn2+, Fe2+, and Fe3+ cations in the inverse spinel AB2O4 crystal lattice. The improved magnetic properties were leveraged to develop T1-weighted MRI contrast agent that are more biocompatible and efficient than currently used Gd-based complexes. This work underscores the rich opportunities in magnetic spinels for not only unusual applications as in MRI contrast enhancement but also the complexity and versatility of its crystal chemistry that forms the basis for its diverse properties.

A novel Gd3+ DTPA-bisamide complex with high relaxivity as an MRI contrast agent.

A novel Gd(III) complex-based magnetic resonance imaging (MRI) contrast agent GdL has been designed and synthesized, which exhibited a much higher relaxivity (7.8 mM-1 s-1) than the commercially used Magnevist® (3.5 mM-1 s-1), good water solubility (>100 mg mL-1), excellent thermodynamic stability (log KGdL = 17.21 ± 0.27), high biosafety and biocompatibility. In particular, the relaxivity of GdL increased to 26.7 mM-1 s-1 in a 4.5% bovine serum albumin (BSA) solution at 1.5 T, which was not significant in other commercial MRI contrast agents. The interaction sites and interaction types of GdL and BSA were further demonstrated by molecular docking simulations. Furthermore, the in vivo MRI behaviour was evaluated by using a 4T1 tumour-bearing mouse model. These results suggested that GdL is an excellent T1-weighted MRI contrast agent and has the potential to be applied in clinical diagnosis.

Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging

Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM−1 s−1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.

Tumor microenvironment responsive theranostic agent for enhanced chemo/chemodynamic/photothermal therapy

The specific characteristics of the tumor microenvironment (TME) and monotherapy always lead to poor therapy effects for tumors. Hereby, we have developed a smart multifunctional theranostic agent-SSMID (Se@SiO2@MnO2-ICG/DOX) nanocomposites (NCs) that could intelligently respond to the TME for enhanced chemotherapy/photothermal/chemodynamic therapy guided by magnetic resonance imaging (MRI). The SSMID NCs were composed of indocyanine green (ICG) and doxorubicin hydrochloride (DOX) co-loaded porous Se@SiO2 @MnO2. Under the specific conditions of the TME (slightly acidic, H2O2 and GSH overexpression), the MnO2 NPs were specifically decomposed and then SSMID released Mn2+, DOX and Se, which played roles in chemodynamic therapy (CDT), chemotherapy, protecting normal tissues and inhibiting tumor cells by modulating reactive oxygen species (ROS), respectively. MnO2 reacted with glutathione (GSH) and H2O2 to generate O2 and Mn2+, which alleviated tumor hypoxia to improve chemotherapy and depleted GSH to enhance oxidative stress for chemodynamic therapy. More importantly, SSMID NCs could simultaneously exert the photothermal therapy (PTT) effect with near-infrared laser irradiation and promote the release of Mn2+ and DOX to achieve enhanced chemotherapy/chemodynamic therapy. In addition, the released Mn2+ could be used as a T1-weighted MRI contrast agent to monitor tumor location. The SSMID NCs exhibited a pronounced tumor growth inhibitory effect and promising biological safety, which develop a new method to rationally design nano-theranostic agents with enhanced performance for anti-tumor.

All-in-one approaches for triple-negative breast cancer therapy: metal-phenolic nanoplatform for MR imaging-guided combinational therapy

BackgroundConventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects.ResultsHerein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy.ConclusionsA nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.Graphical

Nanomagnetic hydrogel based on chitosan, hyaluronic acid, and glucose oxidase as a nanotheranostic platform for simultaneous therapeutic and imaging applications

Theranostic platform including therapeutic agent and diagnostics factor is of great interest in the current cancer treatment research. In this study, we constructed a pH-responsive nanomagnetic hydrogel based on chitosan, hyaluronic acid, and glucose oxidase (NMH-CsHA-GOx) as a platform, which represents good performance both as a nanomedicine and as a dual-modal magnetic resonance imaging (MRI) contrast agent. The NMH-CsHA-GOx is a hybrid catalyst that catalyzes a cascade reaction that results in the production of hydroxyl radicals. This leads to the apoptosis and death of cancer cells under the mildly acidic TME. Moreover, the ultrasmall superparamagnetic Fe3O4 NPs act as the T1-weighted and T2-weighted (dual-modal) MRI contrast agents that can be used to identify the cancer cells. The r1 = 6.37, r2 = 27.07/mM/s, and r2/r1 ratio were obtained from MRI relaxivity measurements. The NMH-CsHA-GOx was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). The morphology of the hydrogel and nanomagnetic hydrogel were characterized by Field emission scanning electron microscopy (FESEM). The size and distribution of Fe3O4NPs were studied by Transmission electron microscopy (TEM) and X-ray elemental mapping, respectively. The analysis confirmed the very small size of the Fe3O4 NPs (5–12 nm), which were dispersed uniformly. The NMH-CsHA-GOx represents high selectivity between normal cells (L929 mouse fibroblast cell line) and tumor cells (MCF-7 breast cancer cell line). The pH-sensitive NMH-CsHA-GOx, can produce a controlled amount of hydroxyl radical under the mildly acidic TME.

Continuous synthesis of extremely small-sized iron oxide nanoparticles used for T1-weighted magnetic resonance imaging via a fluidic reactor

Extremely small-sized iron oxide nanoparticles (ESIONPs) with sizes less than 5 nm have shown great promise as T1 contrast agents for magnetic resonance imaging (MRI). However, their facile and scalable production with simultaneously endowed biocompatible surface chemistry remains difficult to be realized. In this study, by using the coprecipitation method implemented in a specially designed gas/liquid mixed phase fluidic reactor, polyglucose sorbitol carboxymethyether (PSC) coated ESIONPs were continuously synthesized with controllable particle sizes ranging from 1.8 to 4 nm. Among the differently sized ESIONPs, the 3.7-nm ESIONPs exhibit the best performance as T1 MRI contrast agent, featuring a high r1 value of 4.11 (mmol L−1)−1 s−1 and low r2/r1 ratio of 7.90 under a clinical 3 T MR scanning, as well as the excellent T1 MRI contrast effect in not only water but also the cellular environment and blood vessel. Furthermore, the ESIONPs possess long-term stability and good dispersity in aqueous dispersions, making them ideal candidates as safe and effective T1-weighted MRI contrast agent for real clinical use.

Synthesis and structural characterization of silica particles doped with Dy and Gd paramagnetic ions as MRI contrast agents

Silica submicronic particles doped with Dy and Gd paramagnetic ions were successfully synthesized by using chemical synthesis based on the modified Stöber method, having potential applications as contrast agents for magnetic resonance imaging (MRI).Structural characterization analyses show an amorphous character of the particles (XRD), good thermal stability (DTA), and spheroid shape (SEM). The integration of paramagnetic ions into the silica network was demonstrated by the TEM, EPR and FTIR spectroscopies.The magnetic resonance (MR) relaxivity examinations of the samples show a high rate of relaxivity for the particles doped with Dy, making them suitable as T2 contrast agent for magnetic resonance imaging. This is in contrast to the results obtained on the particles doped with Gd, which are an effective T1-weighted MRI contrast agent. Notably, if the silica structure incorporates both Gd and Dy the particles are suitable for contrast enhancement in both T1 and T2 weighted images. These characteristics of the samples are also supported by the value of the relaxivity ratio (r2/r1) for the three samples doped with paramagnetic ions. The results confirm the sustainability of MRI contrast agent applications for all three synthesized samples.

A pH-Activatable MnCO3 Nanoparticle for Improved Magnetic Resonance Imaging of Tumor Malignancy and Metastasis.

Engineered magnetic nanoparticles have been extensively explored for magnetic resonance imaging (MRI) diagnosis of a tumor to improve the visibility. However, most of these nanoparticles display "always-on" signals without tumor specificity, causing insufficient contrast and false positives. Here, we provide a new paradigm of MRI diagnosis using MnCO3 nanorhombohedras (MnNRs) as an ultrasensitive T1-weighted MRI contrast agent, which smartly enhances the MR signal in response to the tumor microenvironment. MnNRs would quickly decompose and release Mn2+ at mild acidity, one of the pathophysiological parameters associated with cancer malignancy, and then Mn2+ binds to surrounding proteins to achieve a remarkable amplification of T1 relaxivity. In vivo MRI experiments demonstrate that MnNRs can selectively brighten subcutaneous tumors from the edge to the interior may be because of the upregulated vascular permeation at the tumor edge, where cancer cell proliferation and angiogenesis are more active. Specially, benefiting from the T2 shortening effect in normal liver tissues, MnNRs can detect millimeter-sized liver metastases with an ultrahigh contrast of 294%. The results also indicate an effective hepatic excretion of MnNRs through the gallbladder. As such, this pH-activatable MRI strategy with facility, biocompatibility, and excellent efficiency may open new avenues for tumor malignancy and metastasis diagnosis and holds great promise for precision medicine.

Multimodal Theranostic Cyanine-Conjugated Gadolinium(III) Complex for In Vivo Imaging of Amyloid-β in an Alzheimer's Disease Mouse Model.

Despite the wide use of magnetic resonance imaging (MRI) as a clinical diagnostic tool, there are still no clinically approved MRI contrast agents that can be applied for cerebral Alzheimer's disease (AD) biomarker imaging. We report here the design and development of the first amyloid-β (Aβ)-targeted, blood-brain barrier (BBB) penetrable theranostic Gd(DOTA)-cyanine dyad, which was synthesized by the conjugation of Gd(DOTA) complex and carbazole-based cyanine dye by the copper(I)-catalyzed azide-alkyne cycloaddition click reaction for imaging of Aβ in vivo and ex vivo in AD mouse models. This dyad, as a multimodal probe, possesses desirable multifunctional properties, including good biocompatibility, low cytotoxicity, high Aβ selectivity, strong fluorescence enhancement upon binding with Aβ species, good paramagnetic properties, high stability, good BBB penetrability, and fast elimination from the mouse. The longitudinal relaxivity (r1) of the dyad was found to be 4.42 mM-1 s-1 at 3 T, suggesting it to be promising as a T1-weighted MRI contrast agent. The probe has been successfully demonstrated to be able to be applied for one- and two-photon excited fluorescence and magnetic resonance (MR) imaging of Aβ in transgenic mouse models of AD. In addition, it can inhibit Aβ aggregation, protect against toxicity induced by Aβ, and suppress Aβ-induced reactive oxygen species (ROS) production. Our results demonstrate the highly promising theranostic capability of the dyad for diagnosis and therapy of AD and extraordinary potential for MRI of Aβ in humans.

Preparation of Mn2+@PolyDOPA-b-polysarcosine micelle as MRI contrast agent with high longitudinal relaxivity

Magnetic resonance imaging (MRI) is a promising technique widely used in clinical diagnose. Poly(α-amino acid)s are excellent carriers for MRI due to their excellent biocompatibility. PDOPA-b-PSar copolymers (defined as “DoS”) are synthesized by sequential polymerizations of 3,4-dihydroxy-L-phenylalanine N-thiocarboxyanhydride (DOPA-NTA) and sarcosine N-thiocarboxyanhydride (Sar-NTA) initiated by neopentylamine in tetramethylene sulfone. Mn2+@DoS micelles have been prepared as T1-weighted MRI contrast agents according to efficient coordination between catechol units and Mn2+ cation. High longitudinal relaxivity (27.7 mM−1·s−1) of Mn2+@PDOPA12-b-PSar72 was observed, and the aqueous micelle exhibits effective MRI contrast enhancement in vivo of nude mice. Mn2+@DoS shows potential clinical application in diagnostic radiology as a novel MRI contrast agent. Gd3+@DoS micelles are also investigated presenting a longitudinal relaxivity of 16.4 mM−1·s−1. Unfortunately, the Gd3+ loading percentage is quite low as 19%.

Ellagic acid–Fe nanoscale coordination polymer with higher longitudinal relaxivity for dual-modality T1-weighted magnetic resonance and photoacoustic tumor imaging

Dual-modality contrast agents for T1-weighted magnetic resonance imaging (MRI) and photoacoustic imaging have attracted substantial attention as they combine the advantages of unlimited penetration depth and high sensitivity. However, most of the reported agents are Gd-based materials that exhibit nephrotoxicity, and few studies have focused on Fe-based materials owing to their lower relaxivity. This work describes the development of an ellagic acid (EA)–Fe nanoscale coordination polymer with high longitudinal relaxivity and strong near-infrared absorption for dual-modality T1-weighted MRI and photoacoustic imaging. The longitudinal relaxivity (r1) of the prepared EA-Fe@BSA nanoparticles was 2.54 mM−1 s−1, an increase of 185% compared with previously reported gallic acid-Fe nanoparticles. Furthermore, in vitro and in vivo experiments demonstrate that the EA-Fe@BSA NPs are an excellent T1-weighted MRI and photoacoustic dual-modality contrast agent with the advantages of convenient synthesis and low toxicity, exhibiting great potential for clinical use in tumor imaging.

Engineering the surface of Gd2O3 nanoplates for improved T1-weighted magnetic resonance imaging

The oleic acid (OA) and oleylamine (OM)-capped Gd2O3 nanoplates were encapsulated into N-Dodecyl-PEI-PEG polymer to synthesize the hydrophilic clusters for T1-weighted magnetic resonance imaging (MRI). The obtained Gd2O3@N-Dodecyl-PEI-PEG clusters showed a hydrodynamic size of 95 nm and a r1 value of 14.13 mM−1 s−1, which was approximately 4 times greater than that of the commercial product gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) (r1 = 3.40 mM−1 s−1). The in vitro toxicity demonstrated that the obtained clusters were biocompatible. The MRI experiments on SCC-7 cells/xenograft tumors indicated that the clusters had obvious T1-enhancement ability. These clusters have great potential application as T1-weighted MRI contrast agents.

Fluorine and Nitrogen Co-Doped Carbon Dot Complexation with Fe(III) as a T1 Contrast Agent for Magnetic Resonance Imaging.

Commercial gadolinium-based materials have been widely used as contrast agents for magnetic resonance imaging (MRI), but the high toxicity of leaking free Gd3+ ions still raises biosafety concerns. Here, we develop a novel, safe, and efficient MRI contrast agent based on a stable Fe(III) complex of fluorine and nitrogen co-doped carbon dots (F,N-CDs) that was prepared from glucose and levofloxacin by a simple microwave-assisted thermal decomposition method. The obtained Fe3+@F,N-CD complex exhibits higher longitudinal relaxivity ( r1 = 5.79 mM-1·s-1) than that of the control samples of the Fe3+@CD complex ( r1 = 4.23 mM-1 s-1) and free Fe3+ ( r1 = 1.59 mM-1 s-1) in aqueous solution, as assessed by a 1.5 T NMR analyzer. More importantly, the Fe3+@F,N-CD complex is very stable with a large coordination constant of 1.06 × 107 in aqueous medium. While incubated with HeLa cells, the Fe3+@F,N-CD complex shows clear MR images, demonstrating that it has potential to be an excellent MRI contrast agent. Furthermore, in vivo MRI experiments indicate that the Fe3+@F,N-CD complex provides high-resolution MRI pictures of 4T1 tumor bearing BALB/c mice 15 min after injection and can be completely excreted 2 h after administration. No cytotoxicity was observed with F,N-CDs and Fe concentration up to 0.2 mg/mL and 0.3 mM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, respectively. The possible mechanism of the enhanced MRI effect of the Fe3+@F,N-CD complex is therefore proposed. The extremely low toxicity, high r1 relaxivity, strong photoluminescence, and low synthetic cost enable the Fe3+@F,N-CD complex to be a safe and promising T1-weighted MRI contrast agent for clinical applications.

One-pot Synthesis of PEGylated Gd-based Nanoparticles as High-performance and Biocompatibility Contrast Agents for T1-Weighted Magnetic Resonance Imaging In vivo

Polyethylene glycol modified(PEGylated) NaGdF4(PEG-NaGdF4) nanoparticles as a novel T1-weighted magnetic resonance imaging(MRI) contrast agent was successfully constructed by a one-pot hydrothermal synthesis method. Because of the functionalization of PEG, the nanoprobes had excellent dispersity, excellent stability and high biocompatibility. More importantly, the as-prepared PEG-NaGdF4 nanoprobes revealed the high longitudinal relaxivity value and prominent T1-weighted MRI contrast performance, which was superior to the commercial MRI contrast agents. With the facile synthesis, excellent dispersity, outstanding stability, remarkable contrast performance and high biocompatibility, the PEGylated NaGdF4 nanoparticles brought more opportunities to the new generation of nanoparticulate-based T1-weighted MRI contrast agents in clinic.

MnO nanoparticles with potential application in magnetic resonance imaging and drug delivery for myocardial infarction.

BackgroundMyocardial infarction (MI) is a leading cause of death worldwide. Therefore, nanoparticles that applied for specific diagnosis of the infarcted area and/or local myocardial delivery of therapeutic agents, are highly desired.Materials and methodsHerein, we developed the MnO-based nanoparticles, with magnetic resonance (MR) and near-infrared fluorescence imaging modalities as an MR imaging contrast agent and potential drug vehicle for the detection and treatment of MI. The chemophysical characteristics, targeting ability toward infarcted myocardium, biodistribution, and biocompatibility of the MnO-based nanoparticles were studied.ResultsIt was found that the MnO-based dual-modal nanoparticles possess high r1 relaxivity and induced no notable in vitro or in vivo toxicity. In a rat model of MI, these nanoparticles represent a very promising MR imaging contrast agent for sensitive and specific detection of the infarcted area, more importantly, without cardiotoxicity, the major defect of conventional Mn-based contrasts. Moreover, ex vivo near-infrared fluorescence imaging indicated that the MnO nanoparticles preferentially accumulate in the infarcted myocardium, which makes them an ideal drug vehicle for MI treatment.ConclusionIn summary, the use of these MnO nanoparticles as a T1-weighted MR imaging contrast agent and potential drug vehicle to target the infarcted myocardium may provide new opportunities for accurate detection of myocardial infarct and treatment of ischemic heart diseases.

Intensely red-emitting luminescent upconversion nanoparticles for deep-tissue multimodal bioimaging

Nowadays, in order to improve the diagnostic accuracy of the disease, more and more contrast agents have been applied in the clinical imaging modalities. A combination of nanotechnology with optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI) has great potential to improve disease diagnosis and therapy. Herein, we developed a novel multimodal contrast agent for deep-tissue bioimaging based on PEGylated Mn2+ doped NaLuF4:Yb/Er nanoparticles (PEG-UCNPs). The multimodal nanoprobes have revealed the intensely red upconversion luminescence emission for deep-tissue upconversion luminescence (UCL) imaging. Moreover, Owing to the high longitudinal relaxivity, the PEG-UCNPs can be used as T1-weighted MRI contrast agents. Additionally, with the high X-ray mass absorption coefficient of Lu3+, the novel nanoprobes are appropriate for CT imaging. With integration the high paramagnetic property, superior X-ray mass absorption coefficient and excellent upconversion luminescence in one system, the multimodal nanoprobes can provide a unique opportunity for MRI, CT and UCL imaging. More importantly, modification with PEG endows the novel nanoprobes with high biocompatibility, which would bring more opportunities for the biomedical applications in clinic.

Gadolinium-Labeled Aminoglycoside and Its Potential Application as a Bacteria-Targeting Magnetic Resonance Imaging Contrast Agent.

Magnetic resonance imaging (MRI) is a powerful diagnostic technique that can penetrate deep into tissue providing excellent spatial resolution without the need for ionizing radiation or harmful radionuclides. However, diagnosing bacterial infections in vivo with clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capabilities, and bacterial penetration and specificity. Here, we report the development of the first gadolinium (Gd)-based bacteria-specific targeting MRI contrast agent, probe 1, by conjugating neomycin, an aminoglycoside antibiotic, with Dotarem (Gd-DOTA, an FDA approved T1-weighted MRI contrast agent). The T1 relaxivity of probe 1 was found to be comparable to that of Gd-DOTA; additionally, probe 1-treated bacteria generated a significantly brighter T1-weighted MR signal than Gd-DOTA-treated bacteria. More importantly, in vitro cellular studies and preliminary in vivo MRI demonstrated probe 1 exhibits the ability to efficiently target bacteria over macrophage-like cells, indicating its great potential for high-resolution imaging of bacterial infections in vivo.

Microwave-assisted preparation of paramagnetic zwitterionic amphiphilic copolymer hybrid molybdenum disulfide for T1-weighted magnetic resonance imaging-guided photothermal therapy.

Magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) has recently attracted tremendous attention. In this study, a paramagnetic zwitterionic amphiphilic copolymer (PZAC) was successfully prepared and utilized as a multifunctional surfactant to form micelles in diethylene glycol to coordinate with a molybdenum disulfide precursor (MoS2). Uniform spherical MoS2 nanohybrids (MoS2@PZAC) were first prepared by a microwave-assisted solvothermal process, which is simpler, easier and more efficient than hydrothermal methods or exfoliation processes. In this nanoplatform, MoS2 serves as a phototherapeutic agent possessing a high photothermal conversion efficiency (33.8%), while PZAC acts as a T1-weighted MRI contrast agent. This nanoplatform has the advantages of ultralow toxicity, prolonged circulation time and bio-imaging guided capability. The cytotoxicity assessment showed the good cytocompatibility of MoS2@PZAC. Furthermore, MoS2@PZAC could effectively kill cancer cells upon 2 W cm-2 808 nm laser irradiation for 10 min in both in vitro and in vivo experiments. This work provides a novel and efficient solution to synthesize a multifunctional and uniform theranostic agent, and the results show that the as-prepared MoS2@PZAC can be used as a promising theranostic agent for T1-weighted MRI-guided PTT of cancer cells.