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Expression of concern for 'Gadolinium embedded iron oxide nanoclusters as T 1 - T 2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery' by Xiaoyong Wang et al. , Nanoscale , 2013, 5 , 8098-8104, https://doi.org/10.1039/C3NR02797J.

Rationale: Sensitive and accurate imaging of cancer is essential for early diagnosis and appropriate treatment. For generally employed magnetic resonance imaging (MRI) in clinic, comprehending how to enhance the contrast effect of T 1 imaging is crucial for improving the sensitivity of cancer diagnosis. However, there is no study ever to reveal the clear mechanism of how to enhance the effect of T 1 imaging and accurate relationships of influencing factors. Herein, this study aims to figure out key factors that affect the sensitivity of T 1 contrast-enhanced MRI (CE-MRI), thereby to realize sensitive detection of tumors with low dose of CAs. Methods: Manganese oxide (MnO) nanoparticles (NPs) with various sizes and shapes were prepared by thermal decomposition. Factors impacting T 1 CE-MRI were investigated from geometric volume, surface area, crystal face to r 2 / r 1 ratio. T 1 CE-MR imaging of liver, hepatic and subcutaneous tumors were conducted with MnO NPs of different shapes. Results: The surface area and occupancy rate of manganese ions have positive impacts on the sensitivity of T 1 CE-MRI, while volume and r 2 / r 1 ratio have negative effects. MnO octahedrons have a high r 1 value of 20.07 mM -1 s -1 and exhibit an excellent enhanced effect in liver T 1 imaging. ZDS coating facilitates tumor accumulation and cellular uptake, hepatic and subcutaneous tumors could be detected with MnO octahedrons at an ultralow dose of 0.4 mg [Mn]/kg, about 1/10 of clinical dose. Conclusions: This work is the first quantitative study of key factors affecting the sensitivity of T 1 CE-MRI of MnO nanoparticles, which can serve as a guidance for rational design of high-performance positive MRI contrast agents. Moreover, these MnO octahedrons can detect hepatic and subcutaneous tumors with an ultralow dose, hold great potential for sensitive and accurate diagnosis of cancer with lower cost, less dosages and side effects in clinic., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Tumor heterogeneity is one major reason for unpredictable therapeutic outcomes, while stratifying therapeutic responses at an early time may greatly benefit the better control of cancer. Here, we developed a hybrid nanovesicle to stratify radiotherapy response by activatable inflammation magnetic resonance imaging (aiMRI) approach. The high Pearson's correlation coefficient R values are obtained from the correlations between the T 1 relaxation time changes at 24-48 h and the ensuing adaptive immunity (R = 0.9831) at day 5 and the tumor inhibition ratios (R = 0.9308) at day 18 after different treatments, respectively. These results underscore the role of acute inflammatory oxidative response in bridging the innate and adaptive immunity in tumor radiotherapy. Furthermore, the aiMRI approach provides a non-invasive imaging strategy for early prediction of the therapeutic outcomes in cancer radiotherapy, which may contribute to the future of precision medicine in terms of prognostic stratification and therapeutic planning.

Background Brain metastases are manually identified during stereotactic radiosurgery (SRS) treatment planning, which is time consuming and potentially challenging. Purpose To develop and investigate deep learning (DL) methods for detecting brain metastasis with MRI to aid in treatment planning for SRS. Materials and Methods In this retrospective study, contrast material-enhanced three-dimensional T1-weighted gradient-echo MRI scans from patients who underwent gamma knife SRS from January 2011 to August 2018 were analyzed. Brain metastases were manually identified and contoured by neuroradiologists and treating radiation oncologists. DL single-shot detector (SSD) algorithms were constructed and trained to map axial MRI slices to a set of bounding box predictions encompassing metastases and associated detection confidences. Performances of different DL SSDs were compared for per-lesion metastasis-based detection sensitivity and positive predictive value (PPV) at a 50% confidence threshold. For the highest-performing model, detection performance was analyzed by using free-response receiver operating characteristic analysis. Results Two hundred sixty-six patients (mean age, 60 years ± 14 [standard deviation]; 148 women) were randomly split into 80% training and 20% testing groups (212 and 54 patients, respectively). For the testing group, sensitivity of the highest-performing (baseline) SSD was 81% (95% confidence interval [CI]: 80%, 82%; 190 of 234) and PPV was 36% (95% CI: 35%, 37%; 190 of 530). For metastases measuring at least 6 mm, sensitivity was 98% (95% CI: 97%, 99%; 130 of 132) and PPV was 36% (95% CI: 35%, 37%; 130 of 366). Other models (SSD with a ResNet50 backbone, SSD with focal loss, and RetinaNet) yielded lower sensitivities of 73% (95% CI: 72%, 74%; 171 of 234), 77% (95% CI: 76%, 78%; 180 of 234), and 79% (95% CI: 77%, 81%; 184 of 234), respectively, and lower PPVs of 29% (95% CI: 28%, 30%; 171 of 581), 26% (95% CI: 26%, 26%; 180 of 681), and 13% (95% CI: 12%, 14%; 184 of 1412). Conclusion Deep-learning single-shot detector models detected nearly all brain metastases that were 6 mm or larger with limited false-positive findings using postcontrast T1-weighted MRI. © RSNA, 2020 See also the editorial by Kikinis and Wells in this issue.

Magnetic resonance imaging (MRI) diagnosis is better assisted by contrast agents that can augment the signal contrast in the imaging appearance. However, this technique is still limited by the inherently low sensitivity on the recorded signal changes in conventional T 1 or T 2 MRI in a qualitative manner. Here, we provide a new paradigm of MRI diagnosis using T 1 - T 2 dual-modal MRI contrast agents for contrast-enhanced postimaging computations on T 1 and T 2 relaxation changes. An albumin-binding molecule (i.e., truncated Evans blue) chelated with paramagnetic manganese ion was developed as a novel T 1 - T 2 dual-modal MRI contrast agent at high magnetic field (7 T). Furthermore, the postimaging computations on T 1 - T 2 dual-modal MRI led to greatly enhanced signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) in both subcutaneous and orthotopic brain tumor models compared with traditional MRI methods. The T 1 - T 2 dual-modal MRI computations have great potential to eliminate suspicious artifacts and false-positive signals in mouse brain imaging. This study may open new avenues for contrast-enhanced MRI diagnosis and holds great promise for precision medicine.

Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multimodal imaging strategies integrating manifold images have improved our ability to diagnose, to guide therapy, and to predict outcomes. Magnetic resonance imaging (MRI) is among the most widely used imaging technique in the clinic and can enable multiparameter anatomical demonstration of diagnosis. Due to the inherent black-and-white production of MR images, however, MRI detection is largely hampered by the occurrence of false-positive diagnoses. In this Perspective, we introduce the paradigm of manipulating the multiparameter MRI, T 1 -T 2 dual-modal MRI, along with enhancement by specific contrast agents. We hope this discussion will promote emerging research interest in T 1 -T 2 dual-modal MRI and provoke the rational design of contrast agents for sophisticated MRI applications.

Tracking of cells in biological systems is critically important for monitoring disease treatment, such as in stem cell therapy. This report prepared new types of biocompatible gadolinium hybrid iron oxide (GdIO) nanocomposites, which demonstrated high sensitivity for dual T 1 - and T 2 -weighted magnetic resonance imaging (MRI). The GdIO nanocomposites could efficiently label mesenchymal stem cells (MSCs) by incubation for 24 h at a safe dose, as they did not affect the cell viability, proliferation or differentiation capacity. There was high contrast enhancement in the GdIO-labeled stem cells for dual T 1 - and T 2 -weighted MR imaging. In addition, the GdIO nanocomposites were injected into adult mouse lateral ventricles, where cells could be labeled to monitor their biological behaviors by MRI. These GdIO nanocomposites with dual-imaging functions are a good platform for cell labeling and other diagnostic applications.

Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation (T 2 ) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2-3 times in the PA and MR imaging, compared with control groups without a magnetic field., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A gadolinium-doped multi-shell upconversion nanoparticle under 800 nm excitation is synthesized with a 10-fold fluorescence-intensity enhancement over that under 980 nm. The nanoformulations exhibit excellent photoacoustic/luminescence/magnetic resonance tri-modal imaging capabilities, enabling visualization of tumor morphology and microvessel distribution at a new imaging depth., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Intermolecular multiple quantum coherences (iMQCs) are a source of MR contrast with applications including temperature imaging, anisotropy mapping, and brown fat imaging. Because all applications are limited by signal-to-noise ratio (SNR), we developed a pulse sequence that detects intermolecular zero quantum coherences with improved SNR., Methods: A previously developed pulse sequence that detects iMQCs, HOMOGENIZED with off resonance transfer (HOT), was modified with a multi-spin echo spatial encoding scheme (MSE-HOT). MSE-HOT uses a series of refocusing pulses to generate a stack of images that are averaged in postprocessing for higher SNR. MSE-HOT performance was quantified by measuring its temperature accuracy and precision during hyperthermia of ex vivo red bone marrow samples., Results: MSE-HOT yielded a three-fold improvement in temperature precision relative to previous pulse sequences. Sources of improved precision were 1) echo averaging and 2) suppression of J-coupling in the methylene protons of fat. MSE-HOT measured temperature change with an accuracy of 0.6°C., Conclusion: MSE-HOT improved the temperature accuracy and precision of HOT to a level that is sufficient for hyperthermia of bone marrow., (© 2015 Wiley Periodicals, Inc.)

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM(-1) s(-1). Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.

Precise nodal staging is particularly important to guide the treatments and determine the prognosis for cancer patients. However, it is still challenging to noninvasively and precisely detect in-depth tumor metastasis in lymph nodes (LNs) because of the small size and high potential of obtaining pseudopositive results. Herein, we report the rational design of a T1-T2 dual-modal MRI contrast agent for accurate imaging of tumor metastasis in LNs using gadolinium-embedded iron oxide nanoplates (GdIOP). The GdIOP were modulated with suitable size in vivo through surface functionalization by zwitterionic dopamine sulfonate (ZDS) molecules. The efficient uptake of GdIOP@ZDS nanoparticles through drainage effect because of the presence of large amount of macrophages and dendritic cells generates both T1 and T2 contrasts in LNs. In contrast, the low uptake of protein-corona-free GdIOP@ZDS nanoparticles by melanoma B16 tumor cells promises pseudocontrast imaging of potential tumor metastasis in LNs. The combination of T1 and T2 imaging modalities allows self-confirmed detection of a metastatic tumor with about 1.2 mm in the minimal dimension in LNs, which is close to the detection limit of submilimeter level of MRI scans. This study provides an efficient and noninvasive strategy to detect tumor metastasis in LNs with greatly enhanced diagnostic accuracy.

Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM(-1) s(-1) with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.

Purpose: Hippocampal volume has been measured and used to separate the people who have Alzheimer disease, stress-related psychiatric disorders such as posttraumatic stress disorder, borderline personality disorder, and schizophrenia from normal people. Owing to the long time to measure the volume of the hippocampus and the difficulty to measure temporal horn, we established standard values of the area, width, and height of hippocampus and temporal horn of the lateral ventricle in certain planes in healthy subjects to aid in the clinical diagnosis., Methods: We measured the area, height, and width of the hippocampus and the temporal horn of the lateral ventricle and the area of both structures in the planes that are perpendicular to the long axis of the hippocampus on magnetic resonance images in 105 healthy subjects., Result: Measured data of hippocampus and temporal horn are presented as mean ± SD. The results of measurement of hippocampus and temporal horn are provided separately., Conclusions: We obtained the reference range in healthy people, and we found that there is a descending trend in area, width, and height of the hippocampus when the planes were taken from mamillary body to interthalamic adhesion. The difference between the 2 sides shows no significance in terms of areas of hippocampus, P > 0.05. However, width and height of the hippocampus have significant difference between the 2 sides except width measured in the plane passing the interthalamic adhesion, P < 0.01. The effect of sex on the values of measurement cannot be obtained, P < 0.01.

We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects. The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect. For example, GdIO nanoparticles with a diameter of ∼4.8 nm exhibited a high r1 relaxivity of 7.85 mM(-1)·S(-1) and a low r2/r1 ratio of 5.24. After being coated with zwitterionic dopamine sulfonate molecules, the 4.8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (∼5.2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption. This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (∼50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging.

Spherical superparamagnetic iron oxide nanoparticles have been developed as T2-negative contrast agents for magnetic resonance imaging in clinical use because of their biocompatibility and ease of synthesis; however, they exhibit relatively low transverse relaxivity. Here we report a new strategy to achieve high transverse relaxivity by controlling the morphology of iron oxide nanoparticles. We successfully fabricate size-controllable octapod iron oxide nanoparticles by introducing chloride anions. The octapod iron oxide nanoparticles (edge length of 30 nm) exhibit an ultrahigh transverse relaxivity value (679.3 ± 30 mM(-1) s(-1)), indicating that these octapod iron oxide nanoparticles are much more effective T2 contrast agents for in vivo imaging and small tumour detection in comparison with conventional iron oxide nanoparticles, which holds great promise for highly sensitive, early stage and accurate detection of cancer in the clinic.

Iron‐based nanomaterials have shown great promise for tumor ferrotherapy in recent years. However, nanoparticle‐induced ferroptosis has low therapeutic efficacy owing to unsatisfactory Fenton reaction activity in a typical tumor microenvironment. In this study, NIR light‐activated Fe/PPy‐RGD nanopolymers were developed to combine photothermal therapy and ferrotherapy and achieve enhanced antitumor activity. Importantly, Fe/PPy‐RGD exhibited excellent therapeutic performance under NIR light activation both in vitro and in vivo. Under irradiation with NIR light, the heat generated by Fe/PPy‐RGD not only induced a therapeutic photothermal effect but also enhanced the release of iron ions and the Fenton reaction by inducing ferroptosis. Additionally, by virtue of RGD conjugation and its ultrasmall size, Fe/PPy‐RGD could effectively accumulate at tumor sites in living mice after systemic administration and could be monitored via MR imaging. Hence, this study provides a promising approach for integrating ferrotherapy with photothermal therapy to achieve enhanced tumor treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Quantitative image analysis of cancers requires accurate tumor segmentation that is often performed manually. In this study, we developed a deep learning model with a self-configurable nnU-Net for fully automated tumor segmentation on serially acquired dynamic contrast-enhanced MRI images of triple-negative breast cancer. In an independent testing dataset, our nnU-Net-based deep learning model performed automated tumor segmentation with a Dice similarity coefficient of 93% and a sensitivity of 96%. Accurate tumor segmentation is required for quantitative image analyses, which are increasingly used for evaluation of tumors. We developed a fully automated and high-performance segmentation model of triple-negative breast cancer using a self-configurable deep learning framework and a large set of dynamic contrast-enhanced MRI images acquired serially over the patients' treatment course. Among all models, the top-performing one that was trained with the images across different time points of a treatment course yielded a Dice similarity coefficient of 93% and a sensitivity of 96% on baseline images. The top-performing model also produced accurate tumor size measurements, which is valuable for practical clinical applications. [ABSTRACT FROM AUTHOR]

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron‐chelating agent with BSA, thus leading to biocompatible and stable Cro‐Fe@BSA nanoparticles (NPs). The Cro‐Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature‐dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat‐induced formation of heat shock proteins and thus the self‐protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro‐Fe@BSA NPs also enabled safe and reliable cancer theranostics. [ABSTRACT FROM AUTHOR]

Using deep learning convolutional neural networks for brain metastasis segmentation in MRI has been a hot topic because a reliable and automated deep learning algorithm with high sensitivity and accuracy can greatly benefit treatment planning for stereotactic radiosurgery. Editorial for "Automated Segmentation of Brain Metastases on T1-Weighted MRI Using Convolutional Neural Network: Impact of Using Volume Aware Loss and Sampling Strategy" Although the study reached high detection sensitivity when using the combination of VA loss and VA sampling, the network had a lesion-averaged Dice similarity coefficient of 0.73, which was not considerably higher than those in other studies. [Extracted from the article]

Abstract: While magnetic resonance imaging contrast agents have potential in noninvasive image‐guided tumor treatment, further developments are needed to increase contrast, biodegradability, and safety. Here, novel engineered manganese‐eumelanin coordination nanocomposites (MnEMNPs) are developed via a facile one‐pot intrapolymerization doping (IPD) approach in aqueous solution, through simple chemical oxidation–polymerization of the 3,4‐dihydroxy‐DL‐phenylalanine precursor with potassium permanganate serving as the Mn source and an oxidant. The resulting MnEMNPs possess ultrahigh longitudinal relaxivity (r1 value up to 60.8 mM−1 s−1 at 1.5 T) attributed to the high manganese doping efficiency (>10%) and geometrically confined conformation. Due to their high manganese chelation stability, excellent biocompatibility, and strong near‐infrared absorption, high‐performance longitudinal‐transverse (T1‐T2) dual‐modal magnetic resonance/photoacoustic imaging and photothermal tumor ablation are achieved. Furthermore, the hydrogen peroxide‐triggered decomposition behavior of MnEMNPs circumvents the poor biodegradation issue of many nanomaterials. This facile, convenient, economical, and efficient IPD strategy will open up new avenues for the development of high‐performance multifunctional theranostic nanoplatforms in bionanomedicine. [ABSTRACT FROM AUTHOR]

Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation ( T2) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2-3 times in the PA and MR imaging, compared with control groups without a magnetic field. [ABSTRACT FROM AUTHOR]

10.1007/s00330-019-06214-8 4 Li Y, Wei D, Liu X. Molecular subtyping of diffuse gliomas using magnetic resonance imaging: comparison and correlation between radiomics and deep learning. Such features include first-order features (for instance pixel intensity mean, median, and histograms), second-order features (for instance texture analysis), and higher order features. [Extracted from the article]

We report a simple strategy to construct a multiple gadolinium complex decorated fullerene (CGDn) as an enhanced T1 contrast agent. The CGDn exhibits much higher T1 relaxivity (∼49.7 mM−1 s−1) than individual Gd-DOTA, and shows excellent T1 contrast enhancement ability both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The effort of incorporating therapeutic drugs with imaging agents has been one of the mainstreams of nanomedicine, which holds great promise in cancer treatment in terms of monitoring therapeutic drug activity and evaluating prognostic index. However, it is still technically challenging to develop nanomedicine endowing a spatiotemporally controllable mechanism of drug release and activatable imaging capability. Here, we developed a yolk-shell type of GSH-responsive nanovesicles (NVs) in which therapeutic drug (Doxorubicin, DOX) and magnetic resonance imaging (MRI) contrast agent (ultrasmall paramagnetic iron oxide nanoparticles, USPIO NPs) formed complexes (denoted as USD) and were encapsulated inside the NVs. The formation of USD complexes is mediated by both the electrostatic adsorption between DOX and poly(acrylic acid) (PAA) polymers and the DOX-iron coordination effect on USPIO NPs. The obtained USD NVs showed a unique yolk-shell structure with restrained drug activity and quenched T 1 MRI contrast ability which, on the other hand, can respond to glutathione (GSH) and lead to drug release and T 1 contrast activation in a spatiotemporally concurrent manner. Furthermore, the USD NVs exhibited great potential to kill HCT116 cancer cells in vitro and effectively inhibit the tumor growth in vivo. This study may shed light on the design of sophisticated nanotheranostics in precision nanomedicine. Image 1 [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size. In this study, we developed a kind of novel BBB-transportable nanomaterials smaller than 14 nm for high-efficiency theranostics of GBM (i.e. , high contrast magnetic resonance imaging (MRI) and radiosensitization of GBM). Typically, poly(acrylic acid) (PAA) stabilized extremely small gadolinium oxide nanoparticles with modification of reductive bovine serum albumin (ES-GON-rBSA) was synthesized in water phase, resulting in excellent water-dispersibility. RGD dimer (RGD2, Glu-{Cyclo[Arg-Gly-Asp-(D-Phe)-Lys]} 2) and lactoferrin (LF) were then conjugated to the ES-GON-rBSA to obtain composite nanoparticle ES-GON-rBSA-LF-RGD2 with extraordinary relaxivities (r 1 = 60.8 mM−1 s−1, r 2 / r 1 = 1.1). The maximum signal enhancement (ΔSNR) for T 1 -weighted MRI of tumors reached up to 423 ± 42% at 12 h post-injection of ES-GON-rBSA-LF-RGD2, which is much higher than commercial Gd-chelates (<80%). ES-GON-rBSA-LF-RGD2 exhibited high biocompatibility and can transport across the in vitro BBB model and the in vivo BBB of mice due to its small particle size (d h = 13.4 nm) and LF receptor mediated transcytosis. Orthotopic GBM studies reinforce that ES-GON-rBSA3-LF-RGD2 can accumulate in the orthotopic GBM and enhance the radiation therapy of GBM as an effective radiosensitizing agent. [ABSTRACT FROM AUTHOR]