T1-weighted Magnetic Resonance Imaging Contrast Research Articles

A self-assembled theranostic nanoplatform for efficient tumor sonodynamic-gas therapy

The powerful antioxidant system in tumor tissues limits the efficacy of sonodynamic therapy (SDT) by reducing the availability of the produced reactive oxygen species (ROS). To address this problem, a pH/ultrasound (US) responsive theranostic nanoplatform is elaborately constructed by self-assembly of nitrogen-doped graphene quantum dots (NGQDs), benzothiazole sulfinate (BTS), Gd3+ ions and poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG). The NGQD component with excellent sonodynamic activity wrapped in the resulting Gd-NGQDs/BTS@PLGA-PEG can efficaciously respond to ultrasonic irradiation and cause abundant ROS generation. Importantly, in response to acidic tumor microenvironment, the loaded BTS sustainably releases SO2, which induces the increase of intracellular •O2− level by inhibiting superoxide dismutase activity and further promotes the enrichment of ROS by reducing intracellular glutathione level and suppressing glutathione peroxidase 4 activity. The well-designed SO2 gas therapy-enhanced SDT strategy leads to high oxidative stress in tumor cells and effective inhibition of the growth of bilateral tumors with only a single intravenous injection of the nanomedicine and a subsequent single US irradiation. Gd-NGQDs/BTS@PLGA-PEG can also be employed as a good T1-weighted magnetic resonance imaging contrast agent to guide tumor therapy. This innovative therapeutic strategy developed in our contribution may provide a new paradigm for the exploration of deep tumor therapy.

Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T1-weighted magnetic resonance imaging contrast agent

To overcome the problems of commercial magnetic resonance imaging (MRI) contrast agents (CAs) (i.e., small molecule Gd chelates), we have proposed a new concept of Gd macrochelates based on the coordination of Gd3+ and macromolecules, e.g., poly(acrylic acid) (PAA). To further decrease the r2/r1 ratio of the reported Gd macrochelates that is an important factor for T1 imaging, in this study, a superior macromolecule hydrolyzed polymaleic anhydride (HPMA) was found to coordinate Gd3+. The synthesis conditions were optimized and the generated Gd-HPMA macrochelate was systematically characterized. The obtained Gd-HPMA29 synthesized in a 100 L of reactor has a r1 value of 16.35 mM−1 s−1 and r2/r1 ratio of 2.05 at 7.0 T, a high Gd yield of 92.7% and a high product weight (1074 g), which demonstrates the feasibility of kilogram scale facile synthesis. After optimization of excipients and sterilization at a high temperature, the obtained Gd-HPMA30 formulation has a pH value of 7.97, osmolality of 691 mOsmol/kg water, density of 1.145 g/mL, and viscosity of 2.2 cP at 20 ℃ or 1.8 cP at 37 ℃, which meet all specifications and physicochemical criteria for clinical injections indicating the immense potential for clinical applications.Graphical

Improving Magnetic Resonance Imaging and Chemodynamic Therapy Properties via Tuning the Fe(II)/Fe(III) Ratio in Hydrophilic Single-Atom Nanobowls.

We developed an intrinsic hydrophilic single-atom iron nanobowl (Fe-SANB) for magnetic resonance imaging (MRI)-guided tumor microenvironment-triggered cancer therapy. Benefiting from the sufficient exposure of Fe single atoms and the intrinsic hydrophilicity of the bowl-shaped structure, the Fe-SANBs exhibited a superior performance for T1-weighted MRI with an r1 value of 11.48 mM-1 s-1, which is 3-fold higher than that of the commercial Gd-DTPA (r1 = 3.72 mM-1 s-1). After further coembedding Gd single atoms in the nanobowls, the r1 value can be greatly improved to 19.54 mM-1 s-1. In tumor microenvironment (TME), the Fe-SANBs can trigger pH-induced Fenton-like activity to generate highly toxic hydroxyl radicals for high-efficiency chemodynamic therapy (CDT). Both the MRI and CDT efficiency of these nanobowls can be optimized by tuning the ratio of Fe(II)/Fe(III) in the Fe-SANBs via controlling the calcination temperature. Furthermore, the generation of •OH at the tumor site can be accelerated via the photothermal effect of Fe-SANBs, thus promoting CDT efficacy. Both in vitro and in vivo results confirmed that our nanoplatform exhibited high T1-weighted MRI contrast, robust biocompatibility, and satisfactory tumor treatment, providing a potential nanoplatform for MRI-guided TME-triggered precise cancer therapy.

The value of T2-weighted MRI contrast ratio combined with DWI in evaluating the pathological grade of solid lung adenocarcinoma

To assess the predictive value of T2-weighted (T2W) magnetic resonance imaging (MRI) in combination with diffusion-weighted imaging (DWI) for determining the pathological grading of solid lung adenocarcinoma. The clinical and imaging data from 153 cases of solid lung adenocarcinoma (82 men, 71 women, mean age 63.2 years) confirmed at histopathology in The First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to May 2022 were analysed retrospectively. Adenocarcinomas were classified into low-grade (G1 and G2) and high-grade (G3) groups following the 2020 pathological grading system proposed by the International Association for the Study of Lung Cancer. The T2-weighted contrast ratio (T2CR), calculated as the T2 signal intensity of the lung mass/nodule divided by the T2 signal intensity of the right rhomboid muscle was utilised. Two experienced radiologists reviewed the MRI images independently, measured the T2CR, and obtained apparent diffusion coefficient (ADC) values. The Mann-Whitney U-test was used to compare general characteristics (sex, age, maximum diameter), T2CR, and ADC values between the low-grade and high-grade groups. The non-parametric Kruskal-Wallis test determined differences in T2CR and ADC values among the five adenocarcinoma subtypes. Receiver characteristic curve (ROC) analysis, along with area under the curve (AUC) calculation, assessed the effectiveness of each parameter in distinguishing the pathological grade of lung adenocarcinoma. A Z-test was used to compare the AUC values. Among the 153 patients with adenocarcinoma, 103 had low-grade adenocarcinoma, and 50 had high-grade adenocarcinoma. The agreement between T2CR and ADC observers was good (0.948 and 0.929, respectively). None of the parameters followed a normal distribution (p<0.05). The ADC value was lower in the high-grade adenocarcinoma group compared to the low-grade adenocarcinoma group (p=0.004), while the T2CR value was higher in the high-grade group (p=0.011). Statistically significant differences were observed in maximum diameter and gender between the two groups (p<0.001 and p=0.005, respectively), while no significant differences were noted in age (p=0.980). Among the five adenocarcinoma subtypes, only the lepidic and micropapillary subtypes displayed statistical differences in ADC values (p=0.047), with the remaining subtypes showing no statistical differences (p>0.05). The AUC values for distinguishing high-grade adenocarcinoma from low-grade adenocarcinoma were 0.645 for ADC and 0.627 for T2CR. Combining T2CR, ADC, sex, and maximum diameter resulted in an AUC of 0.778, sensitivity of 70%, and specificity of 75%. This combination significantly improved diagnostic efficiency compared to T2CR and ADC alone (p=0.008, z=2.624; p=0.007, z=2.679). The MRI quantitative parameters are useful for distinguishing the pathological grades of solid lung adenocarcinoma, offering valuable insights for precise lung cancer treatment.

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.

Holmium (III)-doped multifunctional nanotheranostic agent for ultra-high-field magnetic resonance imaging-guided chemo-photothermal tumor therapy

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T2-weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10−13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. Statement of significanceUltra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T2 MRI properties (r2 = 152.13 mM−1s−1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment.

Employing single valency polyphenol to prepare metal-phenolic network antitumor reagents through FeOOH assistance.

Metal-phenolic networks (MPNs) have been conventionally formed by the coordination of metal ions and polyphenols, which can responsively release metal ions and polyphenols under the trigger of tumor microenvironment (TME), showing high potential in the field of antitumor. However, MPNs are mainly limited to multi-valency polyphenols, and the unavailability of single valency polyphenols greatly hinders their applications even though they have excellent antitumor activity. Herein, we demonstrate a FeOOH assisted preparation method for MPNs antitumor reagent by introducing the complexes of Fe3+, H2O and polyphenol (Fe(H2O)x-polyphenoly) in the preparation process, which overcomes the shortage of single valency polyphenols. Taking apigenin (Ap) as an example, Fe(H2O)x-Apy complexes are foremost formed, in which the Fe(H2O)x is capable of hydrolyzing to generate FeOOH, thus producing Fe3+-Ap networks-coated FeOOH nanoparticles (FeOOH@Fe-Ap NPs). Under the stimulation of the TME, FeOOH@Fe-Ap NPs could release Fe2+ and Ap, realizing ferroptosis and apoptosis for tumor combination therapy. In addition, FeOOH can shorten transverse relaxation time, acting as a T2-weighted magnetic resonance imaging contrast agent. The current efforts provide an alternative strategy for constructing MPNs by exploiting single valency polyphenols, which strengthens the potential of MPNs in antitumor applications.

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.

Reduction of Reactive Oxygen Species Accumulation Using Gadolinium-Doped Ceria for the Alleviation of Atherosclerosis.

Atherosclerosis is a common cardiovascular disease with increasing morbidity and mortality. The pathogenesis of atherosclerosis is strongly related to endothelial dysfunction, which is induced by severe oxidative stress damage derived from reactive oxygen species (ROS). Thus, ROS plays a critical role in the pathogenesis and progression of atherosclerosis. In this work, we demonstrated that the gadolinium doping of CeO2 (Gd/CeO2) nanozymes as effective ROS scavengers delivered high performance for antiatherosclerosis. It was found that the chemical doping of Gd promoted the surface proportion of Ce3+ in the nanozymes and thereby enhanced the overall ROS scavenging ability. In vitro and in vivo experiments unambiguously showed that the Gd/CeO2 nanozymes efficiently scavenged harmful ROS at the cellular and histological levels. Further, Gd/CeO2 nanozymes were demonstrated to significantly reduce vascular lesions by reducing lipid accumulation in macrophage and decreasing inflammatory factor levels, thereby inhibiting the exacerbation of atherosclerosis. Moreover, Gd/CeO2 can serve as T1-weighted magnetic resonance imaging contrast agents, which can generate sufficient contrast to distinguish the location of plaque during living imaging. Through those efforts, Gd/CeO2 may serve as a potential diagnostic and treatment nanomedicine for the ROS-induced atherosclerosis.

Synthesis of Multi-Stimuli Responsive Fe3O4 Coated with Diamonds Nanocomposite for Magnetic Assisted Chemo-Photothermal Therapy

Nanodiamonds with magnetic resonance imaging (MRI) and targeted drug delivery to exert combined effects for biomedical applications have been considered to be an urgent challenge. Herein, a novel bio-nanoarchitectonics (Fe3O4@NDs) with simultaneous imaging and therapeutic capacities was fabricated by covalently conjugating nanodiamonds (NDs) with Fe3O4. Fe3O4@NDs exhibited better biocompatibility and excellent photothermal stability with superb photothermal conversion performance (37.2%). Fe3O4@NDs has high doxorubicin (DOX) loading capacity (193 mg/g) with pH and NIR-responsive release characteristics. Fe3O4@NDs loading DOX showed a combined chemo-photothermal inhibitory effect on the tumor cells. Enhanced T2-weighted MRI contrast toward the tumor, with the assistance of a magnetic field, convinced the Fe3O4@NDs gathered in the tumor more efficiently and could be used for MRI-based cancer diagnosis. Our results revealed an effective strategy to achieve a stimuli-sensitive nanoplatform for multifunctional theranostics by the combined action.

The adjacent effect between Gd(III) and Cu(II) in layered double hydroxide nanoparticles synergistically enhances T1-weighted magnetic resonance imaging contrast.

Magnetic resonance imaging (MRI) is one key technology in modern diagnostic medicine. However, the development of high-relaxivity contrast agents with favorable properties for imaging applications remains a challenging task. In this work, dual Gd(III) and Cu(II) doped-layered double hydroxide (GdCu-LDH) nanoparticles show significantly higher longitudinal relaxivity compared with sole-metal-based LDH (Gd-LDH and Cu-LDH) nanoparticles. This relaxation enhancement in GdCu-LDH is also much greater than the simple addition of the relaxivity rate of the two paramagnetic ions in Gd-LDH and Cu-LDH, presumably attributed to synergistic T1 shortening between adjacent Gd(III) and Cu(II) in the LDH host layers (adjacent effect). Moreover, our GdCu-LDH nanoparticles exhibit a pH-ultrasensitive property in MRI performance and show much clearer MR imaging for tumor tissues in mice than Gd-LDH and Cu-LDH at the equivalent doses. Thus, these novel Gd/Cu-co-doped LDH nanoparticles provide higher potential for accurate cancer diagnosis in clinic application. To the best of our knowledge, this is the first report that two paramagnetic metal ions in one nanoparticle synergistically improve the T1-MRI contrast.

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.

Fe3O4 Nanoparticles Embedded in Pectin–Doxorubicin Composites as pH-Responsive Nanoplatforms for Tumor Diagnosis and Therapy by T1-Weighted Magnetic Imaging

Multifunctional nanomaterials with diagnostic and therapeutic capabilities offer promising customized nanomedicines for cancers. However, achieving good execution of these functions in vivo employing a single nanoframework remains challenging, and only a few of these magnetic nanocarriers have been validated for clinical use. In this study, based on biocompatibility and remarkable multifunctionalities, we describe a novel approach to synthesize small Fe3O4 nanoparticles conjugated with natural polysaccharide pectin and assembled into a pH-responsive T1-weighted magnetic resonance imaging contrast agent, Fe3O4@PD, for better chemotherapeutic efficacy. In vitro studies revealed that the conjugated doxorubicin (DOX) was quickly released in the tumor microenvironment by cleavage of the acid-sensitive acylhydrazone bond at a release rate of 89.72% and exerted a considerable inhibitory effect on breast cancer cells. In vivoT1-weighted images of mice showed that Fe3O4@PD displayed darkening to brightening contrast enhancement at tumor sites, and the relative signal-to-noise ratio of the tumor site reached its maximum (increased to about 2.27-fold) for distinguishing the normal and tumor tissues. Thus, this Fe3O4@PD-based system has the potential to be a multifunctional nanodrug delivery system, and as a smart theragnostic platform, it has broad application prospects in clinical and biological works, such as cell-based diagnostics and in vivo medication monitoring.

Fabrication and Pulse Sequences Evaluation of Iron Oxides Nanoparticles as MRI Contrast Agent

The objective of this in vivo study is to enhance the T2-weighted MRI contrast using superparamagnetic nanoparticles in liver and spleen of rabbits for biomedicine application. Superparamagnetic nanoparticles were synthesized using co-precipitation method. Superparamagnetic nanoparticles were characterized using SEM, EDX, VSM, magnetic resonance relaxation and magnetic resonance imaging (MRI). T1 and T2 relaxations were measured as function of concentration of contrast agents in liver and spleen. High relaxivity ratio r2/r1 showed the efficacy of prepared T2- weighted MRI contrast agent. Rabbits were anesthetized using xylazine and ketamine salts for medical procedure. Ketamine and xylazine were injected with the dose rate of ketamine 25-40 mg/kg and xylazine 2.5-5mg/kg intra-muscularly for veterinary anesthesia. MRI of albino rabbits was executed at 0.35 Tesla using magnetic nanoparticles. FDA approved, 0.2 ml/kg dose of contrast agents was injected in rabbits for MRI scanning. MRI axial and coronal, T1-W and T2-W images of liver and spleen were taken using Spin Echo (SE) at TE=92 and TR=551 and STIR at TE=24 and TR=5170. Spin software was used to estimate the intensity of signal in region of interest induced by magnetic contrast agent. In vivo, MRI study of magnetic contrast agents demonstrated the high T2 -weighted contrast on MRI images of liver and spleen of rabbits. This research also concludes that superparamagnetic nanoparticles may be used as MRI contrast agents for biomedicine application to see the pathology of living organs even at low tesla field.

Theranostic Applications of an Ultra-Sensitive T1 and T2 Magnetic Resonance Contrast Agent Based on Cobalt Ferrite Spinel Nanoparticles.

Simple SummaryMagnetic nanoparticles (MNPs) represent an important class of nanomaterials that has been actively employed in multiple technological applications. The MNPs and their based composites have been intensively developed for magnetic resonance imaging, targeted drug delivery, magnetic hyperthermia, and other applications. Magnetic Resonance Imaging (MRI) has a prominent position among clinical imaging modalities as it allows for high spatial resolution and tissue specificity without harmful ionizing radiation. The aim of the study was the demonstration of the potential use of magnetic nanoparticles based on cobalt ferrite spinel as advanced MRI contrast agents that are capable of both T1-weighted positive and T2-weighted negative contrast enhancements in vitro and in vivo. Furthermore, in the present study, we combined novel physical, chemical, and biomedical approaches to develop a multifunctional MRI-detectable drug delivery system that was an efficient T1- and T2-weighted MRI contrast agent and a nanocarrier for targeted drug delivery in vivo.Nano-dimensional materials have become a focus of multiple clinical applications due to their unique physicochemical properties. Magnetic nanoparticles represent an important class of nanomaterials that are widely studied for use as magnetic resonance (MR) contrast and drug delivery agents, especially as they can be detected and manipulated remotely. Using magnetic cobalt ferrite spinel (MCFS) nanoparticles, this study was aimed at developing a multifunctional drug delivery platform with MRI capability for use in cancer treatment. We found that MCFS nanoparticles demonstrated outstanding properties for contrast MRI (r1 = 22.1 s–1mM–1 and r2 = 499 s–1mM–1) that enabled high-resolution T1- and T2-weighted MRI-based signal detection. Furthermore, MCFS nanoparticles were used for the development of a multifunctional targeted drug delivery platform for cancer treatment that is concurrently empowered with the MR contrast properties. Their therapeutic effect in systemic chemotherapy and unique MRI double-contrast properties were confirmed in vivo using a breast cancer mouse tumor model. Our study thus provides an empirical basis for the development of a novel multimodal composite drug delivery system for anticancer therapy combined with noninvasive MRI capability.

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.

Multimodal Magnetic Resonance and Photoacoustic Imaging of Tumor-Specific Enzyme-Responsive Hybrid Nanoparticles for Oxygen Modulation.

Multimodal imaging contrast agents for cancer that can not only perform diagnostic functions but also serve as tumor microenvironment-responsive biomaterials are encouraging. In this study, we report the design and fabrication of a novel enzyme-responsive T1 magnetic resonance imaging (MRI) contrast agent that can modulate oxygen in the tumor microenvironment via the catalytic conversion of H2O2 to O2. The T1 contrast agent is a core-shell nanoparticle that consists of manganese oxide and hyaluronic acid (HA)-conjugated mesoporous silica nanoparticle (HA-MnO@MSN). The salient features of the nanoparticle developed in this study are as follows: 1) HA serves as a targeting ligand for CD44-expressing cancer cells; 2) HA allows controlled access of water molecules to the MnO core via the digestion of enzyme hyaluronidase; 3) the generation of O2 bubbles in the tumor by consuming H2O2; and 4) the capability to increase the oxygen tension in the tumor. The r 1 relaxivity of HA-MnO@MSN was measured to be 1.29 mM-1s-1 at a magnetic field strength of 9.4 T. In vitro results demonstrated the ability of continuous oxygen evolution by HA-MnO@MSN. After intratumoral administration of HA-MnO@MSN to an HCT116 xenograft mouse model, T1 weighted MRI contrast was observed after 5h postinjection and retained up to 48h. In addition, in vivo photoacoustic imaging of HA-MnO@MSN demonstrated an increase in the tumor oxygen saturation over time after i. t. administration. Thus, the core-shell nanoparticles developed in this study could be helpful in tumor-targeted T1 MR imaging and oxygen modulation.

SynthStrip: skull-stripping for any brain image

The removal of non-brain signal from magnetic resonance imaging (MRI) data, known as skull-stripping, is an integral component of many neuroimage analysis streams. Despite their abundance, popular classical skull-stripping methods are usually tailored to images with specific acquisition properties, namely near-isotropic resolution and T1-weighted (T1w) MRI contrast, which are prevalent in research settings. As a result, existing tools tend to adapt poorly to other image types, such as stacks of thick slices acquired with fast spin-echo (FSE) MRI that are common in the clinic. While learning-based approaches for brain extraction have gained traction in recent years, these methods face a similar burden, as they are only effective for image types seen during the training procedure. To achieve robust skull-stripping across a landscape of imaging protocols, we introduce SynthStrip, a rapid, learning-based brain-extraction tool. By leveraging anatomical segmentations to generate an entirely synthetic training dataset with anatomies, intensity distributions, and artifacts that far exceed the realistic range of medical images, SynthStrip learns to successfully generalize to a variety of real acquired brain images, removing the need for training data with target contrasts. We demonstrate the efficacy of SynthStrip for a diverse set of image acquisitions and resolutions across subject populations, ranging from newborn to adult. We show substantial improvements in accuracy over popular skull-stripping baselines – all with a single trained model. Our method and labeled evaluation data are available at https://w3id.org/synthstrip.

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