Dual-modal Contrast Agent Research Articles

Manganese-Based Magnetic Layered Double Hydroxide Nanoparticle: A pH-Sensitive and Concurrently Enhanced T1/T2-Weighted Dual-Mode Magnetic Resonance Imaging Contrast Agent.

The interference effect and lack of selectivity are the bottlenecks for dual-mode magnetic resonance imaging (MRI) contrast agent development. To address these challenges and overcome the single mode imaging contrast limitations, a novel MgMnAl-layered double hydroxide@iron oxide nanoparticle (MgMnAl-LDH@IO NP) has been successfully synthesized as a concurrently enhanced dual-mode contrast agent for MRI of tumor tissues with sensitive pH response and high efficacy. The attachment of iron oxide nanoparticles on the surface of MgMnAl-LDH NPs led to the increased local magnetic field intensity, inducing the concurrent enhancement of both T1 and T2 relaxivity. The in vitro MRI demonstrated that the MgMnAl-LDH@IO NP could act as a pH-sensitive contrast agent for both T1- and T2-weighted MR imaging (r1, 5.67 mM-1 s-1 under pH 5.0 and 1.98 mM-1 s-1 under pH 7.4; r2, 369.12 mM-1 s-1 under pH 5.0 and 225.29 mM-1 s-1 under pH 7.4). The biocompatibility of the dual-mode contrast agent was revealed by the cytotoxicity test on fibroblast cells. Further in vivo dual-mode MR imaging exhibited that the MgMnAl-LDH@IO NP showed clear T1- and T2-weighted MR imaging of tumor tissues in breast-tumor-bearing mice. The facile synthetic method, desirable biocompatibility, sensitive stimuli response, and concurrently enhanced T1/T2 MRI signals both in vitro and in vivo encourage the great potential biomedical and clinical applications of MgMnAl-LDH@IO NP in MR imaging with improved accuracy.

Ultrasound-Magnetic Resonance Imaging Fusion Scheme Based on Non-Negative Matrix Factorization and Dual Modality Contrast Agent

In order to realize the image fusion and improve the quality of the integration, with the aid of dual modality contrast agent (DMCA), a novel fusion method between ultrasound imaging (US) and magnetic resonance imaging (MRI) was put forward in this paper. Due to US’s strong speckle noise, it was an enormous challenge to fuse US with any other modality images. Under the circumstances, DMCA was used in both US and MRI to strengthen the most important information region of interest. Then, because of Rayleigh distribution of US, a self-adaptive weighted non-negative matrix factorization (SWNMF) scheme is constructed to complete the fusion process. In view of the above-mentioned method, the multiple group comparison tests indicated that US-MRI fusion may be a remarkable method for gaining high-quality fusion image.

Noninvasive Monitoring of Allogeneic Stem Cell Delivery with Dual-Modality Imaging-Visible Microcapsules in a Rabbit Model of Peripheral Arterial Disease.

Stem cell therapies, although promising for treating peripheral arterial disease (PAD), often suffer from low engraftment rates and the inability to confirm the delivery success and track cell distribution and engraftment. Stem cell microencapsulation combined with imaging contrast agents may provide a means to simultaneously enhance cell survival and enable cell tracking with noninvasive imaging. Here, we have evaluated a novel MRI- and X-ray-visible microcapsule formulation for allogeneic mesenchymal stem cell (MSC) delivery and tracking in a large animal model. Bone marrow-derived MSCs from male New Zealand White rabbits were encapsulated using a modified cell encapsulation method to incorporate a dual-modality imaging contrast agent, perfluorooctyl bromide (PFOB). PFOB microcapsules (PFOBCaps) were then transplanted into the medial thigh of normal or PAD female rabbits. In vitro MSC viability remained high (79 ± 5% at 4 weeks of postencapsulation), and as few as two and ten PFOBCaps could be detected in phantoms using clinical C-arm CT and 19F MRI, respectively. Successful injections of PFOBCaps in the medial thigh of normal (n = 15) and PAD (n = 16) rabbits were demonstrated on C-arm CT at 1-14 days of postinjection. Using 19F MRI, transplanted PFOBCaps were clearly identified as “hot spots” and showed one-to-one correspondence to the radiopacities on C-arm CT. Concordance of 19F MRI and C-arm CT locations of PFOBCaps with postmortem locations was high (95%). Immunohistological analysis revealed high MSC survival in PFOBCaps (>56%) two weeks after transplantation while naked MSCs were no longer viable beyond three days after delivery. These findings demonstrate that PFOBCaps could maintain cell viability even in the ischemic tissue and provide a means to monitor cell delivery and track engraftment using clinical noninvasive imaging systems.

Magnetite- and Iodine-Containing Nanoemulsion as a Dual Modal Contrast Agent for X-ray/Magnetic Resonance Imaging.

Noninvasive diagnostic by imaging combined with a contrast agent (CA) is by now the most used technique to get insight into human bodies. X-ray and magnetic resonance imaging (MRI) are widely used technologies providing complementary results. Nowadays, it seems clear that bimodal CAs could be an emerging approach to increase the patient compliance, accessing different imaging modalities with a single CA injection. Owing to versatile designs, targeting properties, and high payload capacity, nanocarriers are considered as a viable solution to reach this goal. In this study, we investigated efficient superparamagnetic iron oxide nanoparticle (SPION)-loaded iodinated nano-emulsions (NEs) as dual modal injectable CAs for X-ray imaging and MRI. The strength of this new CA lies not only in its dual modal contrasting properties and biocompatibility, but also in the simplicity of the nanoparticulate assembling: iodinated oily core was synthesized by the triiodo-benzene group grafting on vitamin E (41.7% of iodine) via esterification, and SPIONs were produced by thermal decomposition during 2, 4, and 6 h to generate SPIONs with different morphologies and magnetic properties. SPIONs with most anisotropic shape and characterized by the highest r2/ r1 ratio once encapsulated into iodinated NE were used for animal experimentation. The in vivo investigation showed an excellent contrast modification because of the presence of the selected NEs, for both imaging techniques explored, that is, MRI and X-ray imaging. This work provides the description and in vivo application of a simple and efficient nanoparticulate system capable of enhancing contrast for both preclinical imaging modalities, MRI, and computed tomography.

Radiolabeling and Biodistribution of new dual modality nanoparticle probe in Nuclear Medicine

Introduction: Dual-modality contrast agents, such as radiolabeled nanoparticles, are promising candidates for a number of diagnostic applications, namely SPECT imaging with MR imaging. So the aim of study was evaluating potential of Chitosan-Coated Magnetic Nanoparticles(SPION) labeled with 99mTc as new Dual-modality probes for liver Imaging. Materials and Methods: In this study chitosan particles were coated on SPION and radiolabeled with 99mTc after Purification. The quality control tests including determining particles size, labeling efficiency, stability and Biodistribution study in the mice were performed. Finally MRI and nuclear medicine imaging study in Balb/c mice in 1 and 4 hour after injection of complex were performed. Results: Results showed that the final complex have spherical shape and with average size 255±30nm. The labeling efficiency and stability of complex with 99mTc were 89±6%, 93±6% respectively. Biodistribution study, MRI and nuclear medicine imaging showed high accumulation of Complex in liver. Conclusion: The results showed that the 99mTc-Chitosan coated SPION may be considered as promising Dual-modality probes for liver Imaging.

Large-scale synthesis of monodisperse Prussian blue nanoparticles for cancer theranostics via an "in situ modification" strategy.

BackgroundThe intrinsic properties of Prussian blue (PB) nanoparticles make them an attractive tool in nanomedicine, including magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal therapy (PTT) properties. However, there still remains the challenge of their poor dispersible stability in the physiological environment. In this study, we developed an efficient hydrothermal method to address the poor dispersible stability of PB nanoparticles in the physiological environment.Materials and methodsThe concentration of H+, the mass of polyvinylpyrrolidone (PVP), and iron sources (K3[Fe(CN)6]) are very vital in the preparation of PB nanoparticles. Through exploring the preparation process, optimized PB nanoparticles (OPBs) with excellent physiological stability were prepared. Hydrodynamic diameter and UV-vis absorption properties were measured to verify the stability of the prepared OPBs. Properties of dual-mode imaging, including MRI/PAI, and PTT of OPBs were investigated both in vitro and in vivo. In addition, the in vivo biosafety of OPBs was systematically assessed.ResultsOPBs were stable in different environments including various media, pH, and temperatures for at least 90 days, indicating that they are suitable for biomedical application via intravenous administration and easily stored in a robust environment. Compared with other research into the synthesis of PB nanoparticles, the “in situ modification” synthesis of PB nanoparticles had advantages, including a simple process, low cost, and easy mass preparation. OPBs showed no significant signs of toxicity for 90 days. As a proof of concept, the OPBs served as dual-mode image contrast agents and photothermal conversion agents for cancer diagnosis and therapy both in vitro and in vivo.ConclusionOur findings suggest a facile but efficient strategy with low cost to address the poor dispersible stability of PB nanoparticles in physiological environments. This will promote the development of further clinical transformations of PB nanoparticles, especially in cancer theranostics.

Bandgap Engineered Polypyrrole-Polydopamine Hybrid with Intrinsic Raman and Photoacoustic Imaging Contrasts.

Intrinsically multimodal nanomaterials have revealed their great potential as a new class of contrast agents. We herein report a bandgap engineering strategy to develop an intrinsically Raman-photoacoustic (PA) active probe that is based on semiconducting conjugated polymers. This dual modal probe is prepared by doping a semiconducting conjugated polymer with polydopamine (PDA) through a one-pot reaction. When applied in the polypyrrole (PPy), this strategy can enhance Raman scattering and the PA amplitude of PPy-PDA hybrid by 3.2 and 2.4 times, respectively, so that both signals can be further applied in bioimaging. In the hybrid, such a dual-enhancement effect is achieved by infusing these two macromolecules at the nanoscale to reduce the optical bandgap energy. This work not only introduces a dual modal contrast agent but also provides a new method of manipulating semiconducting polymer's inherent optical features for bioimaging.

Nitroxide-radicals-modified gold nanorods for in vivo CT/MRI-guided photothermal cancer therapy.

PurposeThis article presents a report of the synthesis, characterization, and biomedical application of nitroxide-radicals–modified gold nanorods (Au-TEMPO NRs) for imaging-guided photothermal cancer therapy.Patients and methodsAu nanorods were synthesized through seed-mediated growth method, 4-Amino-TEMPO was added and the reaction proceeded under magnetic stirring.ResultsWith a mean length of 39.2 nm and an average aspect ratio of approximately 3.85, Au-TEMPO NRs showed good photothermal ability when they were irradiated by 808-nm laser. Au-TEMPO NRs could be stored in PBS for more than 1 month, showed no cytotoxicity against both tumor and normal cells at a concentration of up to 3 mg/mL, and functioned as a dual-mode contrast agent for CT/magnetic resonance (MR) imaging in vitro and in vivo, due to their high X-ray attenuation of Au and good r1 relaxivity of nitroxide radicals. Further, they had a long retention time (~4 hours) in the main organs, which enabled a long CT/MR imaging time window for diagnosis. Bio-distribution results revealed that these Au-TEMPO NRs passively aggregated in the liver and spleen. After irradiation by 808-nm laser, Au-TEMPO NRs could ablate the solid tumor in 4T1 tumor-bearing mice, which implied they were a potential theranostic agent for dual-mode imaging and photothermal cancer therapy.ConclusionThis type of Au-TEMPO NRs with the abilities of CT/MR imaging and photothermal therapy, can play an active role in imaging-guided photothermal cancer therapy.

Superparamagnetic graphene quantum dot as a dual-modality contrast agent for confocal fluorescence microscopy and magnetomotive optical coherence tomography.

A magnetic graphene quantum dot (MGQD) nanoparticle, synthesized by hydrothermally reducing and cutting graphene oxide-iron oxide sheet, was demonstrated to possess the capabilities of simultaneous confocal fluorescence and magnetomotive optical coherence tomography (MMOCT) imaging. This MGQD shows low toxicity, significant tunable blue fluorescence and superparamagnetism, which can thus be used as a dual-modality contrast agent for confocal fluorescence microscopy (CFM) and MMOCT. The feasibility of applying MGQD as a tracer of cells is shown by imaging and visualizing MGQD labeled cells using CFM and our in-house MMOCT. Since MMOCT and CFM can offer anatomical structure and intracellular details, respectively, the MGQD for cell tracking could provide a more comprehensive diagnosis.

Folate-receptor-targeted laser-activable poly(lactide-co-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy.

BackgroundCancer is one of the most serious threats to human health. Precision medicine is an innovative approach to treatment, as part of which theranostic nanomedicine has been studied extensively. However, the required biocompatibility and substantial cost for the approval of nanomedicines hinder their clinical translation.PurposeWe designed a novel type of theranostic nanoparticle (NP) folate-receptor-targeted laser-activatable poly(lactide-co-glycolic acid) (PLGA) NPs loaded with paclitaxel (Ptx)/indo-cyanine green (ICG)-folic acid-polyethylene glycol (PEG)-PLGA-Ptx@ICG-perfluorohexane (Pfh)- using safe and approved materials and drugs, which would facilitate clinical translation. With laser irradiation, highly efficient photothermal therapy can be achieved. Additionally, targeted NPs can be activated by near-infrared laser irradiation at a specific region, which leads to the sharp release of Ptx at areas of high folate-receptor expression and ensures a higher Ptx concentration within the tumor region, thereby leading to chemo/photothermal synergistic antitumor efficacy. Meanwhile, the NPs can be used as a dual-modality contrast agent for photoacoustic and ultrasound imaging.Materials and methodsFA-PEG-PLGA-Ptx@ICG-Pfh NPs were prepared by sonification method and characterized for physicochemical properties. Cytotoxicity and in vivo biocompatibility were evaluated respectively by CCK8 assay and blood analysis. NPs as dual-modality contrast agents were evaluated by photoacoustic/ultrasound imaging system in vitro and in vivo. In vitro anticancer effect and in vivo anticancer therapy was evaluated by CCK8 assay and MDA-MB231 tumor-bearing mice model.ResultsFA-PEG-PLGA-Ptx@ICG-Pfh NPs were in the size of 308±5.82 nm with negative zeta potential and showed excellent photothermal effect. The NPs could be triggered sharp release of Ptx by laser irradiation, and showed the good biocompatibility in vitro and in vivo. Through photoacoustic/ultrasound imaging, the NPs showed an excellent ability as dual-modality contrast agents in vitro and in vivo. FA-PEG-PLGA-Ptx@ICG-Pfh NPs with laser irradiation showed the best anticancer efficacy in vitro and in vivo.ConclusionSuch a biocompatible and novel theranostic NP is expected to integrate dual-modality imaging with improved therapeutic efficacy and provide a promising paradigm for cancer therapy.

Silica-coated iron-oxide nanoparticles doped with Gd(III) complexes as potential double contrast agents for magnetic resonance imaging at different field strengths

In the present work, we have prepared the $$\sim $$ 10 nm superparamagnetic iron-oxide nanoparticles by means of high-temperature decomposition of iron oleate precursor. Then they were coated with silica shell to impart water-solubility and an ability to accommodate paramagnetic Gd(III)-based complexes inside silica coating. All of the prepared nanoparticles form stable in time aqueous dispersions and show good negative or/and positive contrasting effect at different magnetic field strengths (0.47, 1.41, 14.1 T). It has been also exemplified that the incorporation of [Gd(TCAS)] complexes into silica shell triggers a significant increase of the transverse relaxivity of the core–shell nanoparticles. The correlation between relaxometric properties and morphology of the obtained nanoparticles was revealed. The non-toxicity of the obtained nanoparticles along with their ability to shorten both transverse and longitudinal relaxation rates of water protons make them good candidates for their use as dual-mode contrast agents in MRI.

Effect of Eu doping concentration on fluorescence and magnetic resonance imaging properties of Gd2O3:Eu3+ nanoparticles used as dual-modal contrast agent

Europium-doped gadolinium oxide (Gd2O3:Eu3+) nanoparticles (NPs) with favorable properties for use in fluorescence imaging (FI) and magnetic resonance imaging (MRI) dual-modal contrast agent has attracted intense attention in biomedical applications. However, limited information is available on balancing FI and MRI by adjusting doping concentrations. In this study, Gd2O3:Eu3+ NPs with various Eu3+ doping concentrations were prepared by the facile and general technique of laser ablation in liquid (LAL). The influence of Eu3+-doping concentration on fluorescence properties and longitudinal relaxivity were investigated. The optimum Eu3+-doping concentration with both high fluorescence properties and longitudinal relaxivity was determined to be 5%. The characterization of the structure, morphology, and composition shows that these NPs possess good crystallinity and excellent dispersibility. These results show that Gd2O3:Eu3+ NPs prepared by LAL are promising candidates for highly efficient FI and MRI dual-modal contrast agents.

T1-T2 molecular magnetic resonance imaging of renal carcinoma cells based on nano-contrast agents.

BackgroundThe development of T1–T2 dual contrast agent (CA) favors the visualization of the lesion in a more accurate and reliable manner by magnetic resonance imaging (MRI). The relaxivity and the interference between T1 and T2 CA are the main concerns for their design.MethodsIn this work, we constructed an Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex where BSA-Gd2O3 NPs and Fe3O4 NPs were chosen as T1 and T2 MRI CAs and a 20 nm mesoporous silica (mSiO2) nanoshell was introduced to reduce the interference between them. We performed transmis sion electron microscopy, X-ray powder diffraction, UV-vis absorption spectra, and Fourier transform infrared absorption (FTIR) spectra to characterize the prepared nanocom-plex and MRI scanning to evaluate their MRI behaviors. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and hematologic and biochemical analyses were introduced to evaluate their in vitro and in vivo toxicity. Finally, the specific MRI of 786-0 cells with Fe3O4@mSiO2/PDDA/BSA-Gd2O3-AS1411 nanoprobe in vitro was realized. In vivo biodistribution of Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in the mouse was determined by the quantification of the Gd element by inductively coupled plasma-mass spectrometry.ResultsThe prepared Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex possessed high longitudinal (r1=11.47 mM s−1 Gd) and transverse (r2=195.1 mM s−1 Fe) relaxivities, enabling its use as a T1–T2 dual contrast agent for MRI. MTT testing and hematologic and biochemical analysis indicated the good biocompatibility of Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in vitro and in vivo. After further conjugation with AS1411 aptamer, they could target tumor cells successfully by T1 and T2 MRI in vitro. The possible metabolic pathway of the tail vein-injected Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in mouse was mainly via kidney.ConclusionA T1–T2 dual-mode contrast agent, Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nano-complex, was developed and its good performance for tumor cell targeting in vitro and kidney contrast-enhanced MRI in mice indicated its promising potential as an effective T1–T2 dual-mode contrast agent for in vivo MRI with self-confirmation.

Surface Design of Eu-Doped Iron Oxide Nanoparticles for Tuning the Magnetic Relaxivity.

Relaxivity tuning of nanomaterials with the intrinsic T1- T2 dual-contrast ability has great potential for MRI applications. Until now, the relaxivity tuning of T1 and T2 dual-modal MRI nanoprobes has been accomplished through the dopant, size, and morphology of the nanoprobes, leaving room for bioapplications. However, a surface engineering method for the relaxivity tuning was seldom reported. Here, we report the novel relaxivity tuning method based on the surface engineering of dual-mode T1- T2 MRI nanoprobes (DMNPs), along with protein interaction monitoring with the DMNPs as a potential biosensor application. Core nanoparticles (NPs) of europium-doped iron oxide (EuIO) are prepared by a thermal decomposition method. As surface materials, citrate (Cit), alendronate (Ale), and poly(maleic anhydride- alt-1-octadecene)/poly(ethylene glycol) (PP) are employed for the relaxivity tuning of the NPs based on surface engineering, resulting in EuIO-Cit, EuIO-Ale, and EuIO-PP, respectively. The key achievement of the current study is that the surface materials of the DMNP have significant impacts on the r1 and r2 relaxivities. The correlation between the hydrophobicity of the surface material and longitudinal relaxivity ( r1) of EuIO NPs presents an exponential decay feature. The r1 relaxivity of EuIO-Cit is 13.2-fold higher than that of EuIO-PP. EuIO can act as T1- T2 dual-modal (EuIO-Cit) or T2-dominated MRI contrast agents (EuIO-PP) depending on the surface engineering. The feasibility of using the resulting nanosystem as a sensor for environmental changes, such as albumin interaction, was also explored. The albumin interaction on the DMNP shows both T1 and T2 relaxation time changes as mutually confirmative information. The relaxivity tuning approach based on the surface engineering may provide an insightful strategy for bioapplications of DMNPs and give a fresh impetus for the development of novel stimuli-responsive MRI nanoplatforms with T1 and T2 dual-modality for various biomedical applications.

A preliminary study of photoacoustic/ultrasound dual-mode imaging in melanoma using MAGE-targeted gold nanoparticles

Nanoprobes are small enough to circulate within the vasculature and can reach tumour tissues through the endothelial gap, providing a new strategy for accurate tumour monitoring and imaging-guided antitumour therapy at the molecular level. Both photoacoustic and ultrasonic imaging are noninvasive tools for cancer detection via the application of nanoprobes. In this study, a polymeric multifunctional nanoparticle probe loaded with gold nanorods (Au-NRs) and liquid perfluorocarbon (perfluorinated hexane/PFH) and conjugated to a monoclonal antibody (MAGE-1 antibody) to melanoma-associated antigens (MAGE) targeting melanoma was successfully prepared by the double emulsion and carbodiimide methods as a targeted photoacoustic/ultrasound dual-mode imaging contrast agent (MAGE-Au-PFH-NPs). Cell-targeting experiments in vitro showed large amounts of MAGE-Au-PFH-NPs surrounding B16 melanoma cells in the targeted group. The photoacoustic signal in the targeted group was significantly increased, and the duration was longer than that in the untargeted group in vivo. The photoacoustic signal of the nanoprobes was enhanced with increased Au-NR concentration in the photoacoustic experiment in vitro. The enhanced signal was observed by ultrasound after 808-nm laser irradiation. A cytotoxicity and biocompatibility test showed that MAGE-Au-PFH-NPs exhibited good biological safety. The MAGE-Au-PFH-NPs can be used as a photoacoustic/ultrasound dual-mode contrast agent to lay the foundation for a promising new approach for the noninvasive targeting, monitoring and treatment of tumours.

Dual-Modality Surface-Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation.

Difficulty in visualizing glioma margins intraoperatively remains a major issue in the achievement of gross total tumor resection and, thus, better clinical outcome of glioblastoma (GBM) patients. Here, the potential of a new combined optical + optoacoustic imaging method for intraoperative brain tumor delineation is investigated. A strategy using a newly developed gold nanostar synthesis method, Raman reporter chemistry, and silication method to produce dual-modality contrast agents for combined surface-enhanced resonance Raman scattering (SERRS) and multispectral optoacoustic tomography (MSOT) imaging is devised. Following intravenous injection of the SERRS-MSOT-nanostars in brain tumor bearing mice, sequential MSOT imaging is performed in vivo and followed by Raman imaging. MSOT is able to accurately depict GBMs three-dimensionally with high specificity. The MSOT signal is found to correlate well with the SERRS images. Because SERRS enables uniquely sensitive high-resolution surface detection, it could represent an ideal complementary imaging modality to MSOT, which enables real-time, deep tissue imaging in 3D. This dual-modality SERRS-MSOT-nanostar contrast agent reported here is shown to enable high precision depiction of the extent of infiltrating GBMs by Raman- and MSOT imaging in a clinically relevant murine GBM model and could pave new ways for improved image-guided resection of brain tumors.

PH-responsive theranostic nanocomposites as synergistically enhancing positive and negative magnetic resonance imaging contrast agents

BackgroundThe rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications. We aimed to afford a potential strategy to pose both T1- and T2-weighted MRI functions, and thereby realizing imaging guided drug delivery and targeted therapy.ResultsTheranostic nanocomposites Mn-porphyrin&Fe3O4@SiO2@PAA-cRGD were fabricated and characterized, and the nanocomposites were effectively used in T1- and T2-weighted MRI and pH-responsive drug release. Fluorescent imaging also showed that the nanocomposites specifically accumulated in lung cancer cells by a receptor-mediated process, and were nontoxic to normal cells. The r2/r1 ratio was 20.6 in neutral pH 7.4, which decreased to 7.7 in acidic pH 5.0, suggesting the NCs could act as an ideal T1/T2 dual-mode contrast agent at acidic environments of tumor. For in vivo MRI, T1 and T2 relaxation was significantly accelerated to 55 and 37%, respectively, in the tumor after i.v. injection of nanocomposites.ConclusionThe synthesized nanocomposites exhibited highly sensitive MRI contrast function no matter in solution, cells or in vivo by synergistically enhancing positive and negative magnetic resonance imaging signals. The nanocomposites showed great potential for integrating imaging diagnosis and drug controlled release into one composition and providing real-time imaging with greatly enhanced diagnostic accuracy during targeted therapy.

Captopril-Loaded Superparamagnetic Nanoparticles as a New Dual-Mode Contrast Agent for Simultaneous In Vitro/In Vivo MR Imaging and Drug Delivery System

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely applied as magnetic resonance imaging (MRI) contrast agents and drug carriers in drug delivery systems (DDSs) for diagnostics and treatment of diseases. Observation of drug delivery, drug release, and monitoring of the treatment can be performed by MRI. Magnetic nanoparticles (MNPs) can be used as dual-mode agents for simultaneous MRI contrast and drug delivery. Application of dual-mode MRI-contrast and drug-carrier agent is especially useful in targeted DDS. In this study, we report on the preparation of captopril-coated MNPs as a new dual-mode agent for simultaneous MRI contrast and DDS. The influence of contrast agent on the longitudinal (T1) and transverse (T2, T2*) relaxation times was studied and it was found that the effect on T2 and T2* exceeds the effect on T1, which leads to darkening of the MR image. Release of captopril from γ-Fe2O3@SiO2@captopril system was studied at three pH values and it was established that the drug release at pH 1.2 was greater than that at pH 4.8 and 7.4. The obtained results show that MNPs loaded with captopril can be used as dual-mode MRI contrast agent and DDS system.

Two-photon graphene quantum dot modified Gd2O3 nanocomposites as a dual-mode MRI contrast agent and cell labelling agent.

For obtaining high-resolution macroscopical anatomical information and high sensitivity microscopical optical signals, it is highly desirable to develop dual-modality magnetic resonance imaging (MRI) and fluorescent probes in medical imaging simultaneously. In this study, Gd2O3 nanoparticles were modified with two-photon graphene quantum dots (GQD), integrating a magnetic resonance imaging (MRI) contrast agent with two-photon imaging functionality into one nanoprobe. A photoluminescence study indicated that the GQD modification process integrated MRI properties with both one-photon and two-photon imaging properties. Gd2O3/GQD nanocomposites showed a significantly improved longitudinal relaxivity (r1 = 15.995 mM-1 s-1) in comparison with commercial Magnevist (Gd-DTPA, r1 = 4.5 mM-1 s-1) and some reported papers. Excellent water solubility and good biocompatibility make Gd2O3/GQD nanocomposites an ideal dual-modal imaging agent, suggesting their potential and significant biological and clinical applications in the future.

Hydrogen peroxide degradable conjugated polymer nanoparticles for fluorescence and photoacoustic bimodal imaging.

Herein we report the preparation of conjugated polymer nanoparticles via in situ Sonogashira polymerization to serve as a H2O2-degradable fluorescence/photoacoustic dual-modality contrast agent for cellular imaging.