Magnetic Resonance Imaging Contrast Research Articles

A Macrocyclic Hybrid PET/MRI Probe for Quantitative Perfusion Imaging In Vivo.

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction, a condition that is typically challenging to diagnose. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for practical synthesis and improved diagnostic accuracy.

One-Pot Fabrication of Kinetically Inert Ultrasmall Manganese(II) Chelate-Backboned Polymer Contrast Agents for High-Performance Magnetic Resonance Imaging.

Traditional macromolecules or nanoscale Mn2+ chelate-based magnetic resonance imaging (MRI) contrast agents (CAs) suffer from complicated and laborious synthesis processes, relatively low kinetic stability and T1 relaxivity, limiting their clinical applications. Herein, we fabricated a series of kinetically inert Mn2+ chelate-backboned polymers, P(MnL-PEG), through a facile and one-pot polymerization process. Particularly, P(MnL-PEG)-3 demonstrates a significantly higher T1 relaxivity of 23.9 Mn mM-1 s-1 at 1.5 T than that of previously reported small molecules and macromolecules or nanoscale Mn2+ chelate-based CAs. Due to its high T1 relaxivity, extended blood circulation, hepatocyte-specific uptake, and kidneys metabolism, P(MnL-PEG)-3 presents significantly enhanced contrast in blood vessel, liver, and kidneys imaging compared to clinical Gd3+-based CAs (Gd-EOB-DTPA and Gd-DOTA) at a dosage of 0.05 mmol Mn/Gd kg-1 BW, and can accurately diagnose orthotopic H22 liver tumors in vivo in animal models. We anticipate that this work will promote the development of clinically relevant MRI CAs.

Dynamic susceptibility contrast‑enhanced perfusion magnetic resonance imaging parameters for predicting MGMT promoter methylation and prognostic value in newly diagnosed patients with glioblastoma.

O6-methylguanine DNA methyltransferase (MGMT) promoter methylation is an important clinical biomarker of newly diagnosed glioblastoma. Previous radiological studies using dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion have aimed to predict MGMT methylation status non-invasively in gliomas with radiological characteristics. The possibility of predicting MGMT methylation status using DSC-MRI perfusion with a radiological approach remains controversial. The present study aimed to evaluate the usefulness of MRI perfusion parameters as non-invasive markers to predict MGMT methylation status and prognosis in newly diagnosed glioblastoma patients. Thus, 50 patients with histologically confirmed primary glioblastoma, IDH-wildtype who underwent tumor resection at Osaka University Hospital (Suita, Japan) between January 2017 and January 2023 were included in this study. The mean cerebral blood volume (CBV) ratio (rCBV) and cerebral blood flow (CBF) ratio (rCBF) for tumors with MGMT methylation (mean rCBV:2.09 and mean rCBF:3.08) were significantly higher compared with those for tumors without MGMT methylation (mean rCBV:1.33 and mean rCBF:1.85; P<0.05). While patients with MGMT methylation had longer progression-free survival (PFS) compared with those without MGMT methylation (P<0.05), there was no significant difference in OS with or without MGMT methylation (P=0.06). By contrast, there was no association between MRI perfusion parameters and OS or PFS in patients with glioblastoma. Furthermore, the association between CBV, CBF, MGMT promotor methylation status, OS, and PFS were explored. There was no significant prognostic difference between low vascularity tumors (rCBV <1.3 or rCBF <1.8) with or without MGMT methylation. On the other hand, high vascularity tumors (rCBF ≥1.8) with MGMT promotor methylation were associated to longer OS and PFS compared with those without. However, there was no association between MGMT methylation status and OS or PFS in patients with high rCBV (rCBV ≥1.3). The present study indicated that CBV and CBF could be used to predict the MGMT methylation status in glioblastomas. However, the prognostic value of tumor vascularity and MGMT methylation status may be limited.

Multifunctional nanoparticles potentiate in-situ tumor vaccines via reversing insufficient Photothermal therapy by disrupting tumor vasculature

Photothermal therapy can trigger immunogenic cell death and release personalized in-situ tumor vaccine, activating immune responses to eliminate systemic tumors beyond the irradiated zone. However, the immune response of the in-situ tumor vaccines is often undermined by the residual tumor cells and their induced immunosuppressive tumor microenvironment (TME), which is attributed to insufficient photothermal effects stemming from the limited accumulation of photosensitizers. To overcome these limitations, we developed multi-functional nanoparticles (VI@Gd-NPs) that integrate a tumor vasculature-specific disrupting agent (Vadimezan, Phase III clinical drug), a photosensitizer (Indocyanine Green, ICG), and a magnetic resonance imaging contrast agent (Gadolinium, Gd) through chemical self-assembly. By selectively disrupting the tumor vasculature, these nanoparticles enhance the intratumoral delivery of photosensitizers (ICG and blood cells), and Gd. With the guidance of Gd-enhanced MRI, the improved delivery facilitates comprehensive photothermal ablation and regulates the TME, further initiating the in-situ tumor vaccine. Notably, this approach significantly enhances anti-tumor immune responses, improves survival rates, and reduces tumor recurrence and metastasis in various animal models. Moreover, depleting CD8+ T cells reverses these therapeutic benefits, highlighting the critical role of adaptive T cell immunity. Therefore, the VI@Gd-NPs treatment holds great potential for reigniting the in-situ tumor vaccine of photothermal therapy.

Hyperpolarized 129Xe Lung MRI and Spectroscopy in Mechanically Ventilated Mice.

Hyperpolarized (HP) xenon-129 (129Xe) is an inhaled magnetic resonance imaging (MRI) contrast agent with unique spectral and physical properties that can be exploited to quantify pulmonary physiology, including ventilation, restricted diffusion (alveolar-airspace size), and gas exchange. In humans, it has been used to evaluate disease severity and progression in a variety of pulmonary disorders and is approved for clinical use in the United States and United Kingdom. Beyond its clinical applications, the ability of 129Xe MRI to noninvasively assess pulmonary pathophysiology and provide spatially resolved information is valuable for preclinical research. Among animal models, mice are the most widely used due to the accessibility of genetically modified disease models. Here, 129Xe MRI is promising as a minimally invasive, radiation-free, and sensitive technique to longitudinally monitor lung disease progression and therapy response (e.g., in drug discovery). This technique can extend to preclinical applications by incorporating an MRI-triggered, free-breathing apparatus or mechanical ventilator to deliver gas. Here, we describe the steps and provide checklists to ensure robust data collection and analysis, including creating a thermally polarized xenon gas phantom for quality control, optimizing polarization, animal handling (sedation, intubation, ventilation, and care for mice), and protocols for ventilation, restricted diffusion, and gas exchange data. While preclinical 129Xe MRI can be applied in various animal models (e.g., rats, pigs, sheep), this protocol focuses on mice due to the challenges posed by their small anatomy, which are balanced by their affordability and the availability of many disease models.

Concurrent photothermal therapy and nuclear magnetic resonance imaging with plasmonic–magnetic nanoparticles: A numerical study

Background and Objective: Theranostics is the combination of the diagnostic and therapeutic phases. Here we focus on simultaneous use of photothermal therapy and magnetic resonance imaging, employing a contrast-photothermal agent that converts incident light into heat and affects the transverse relaxation time, a key magnetic resonance imaging parameter. Our work considers a gold–magnetite nanoshell platform to gauge the feasibility of magnetic resonance imaging monitoring of the heating associated with phototherapy, by studying the modification of the transverse relaxation rate induced by laser illumination of a solution containing these hybrid nanoparticles. Methods:We simulate a system composed of an aqueous solution with hybrid nanoshells under continuous laser irradiation, enabling the evaluation of spatial variations of the transverse relaxation rate within the sample. We work with the hybrid nanoshell platform comprising a metal/gold shell for thermoplasmonic effects and a magnetite core for magnetic resonance imaging contrast enhancement. The optical properties of the nanoshells are first obtained through simulations using the finite element method. Next, the heating generated by the laser illumination is calculated by numerical integration. Finally, the transverse relaxation rate is obtained through the application of an analytical model. Additionally, we conduct an optimization of the nanoshell geometry to fulfill requirements of both magnetic resonance imaging and phototherapy techniques. Results:Our findings demonstrate a narrow range of nanoshell sizes exhibiting both a plasmonic absorption peak in the human biological window and a high response to laser illumination of the transverse relaxation rate. Furthermore, the illumination can induce up to a 30% modification in transverse relaxation rate compared to the non-illuminated scenario in this range of nanoshell sizes. Conclusions:In this work we establish the numerical understanding of the interplay between phototherapy and nuclear magnetic resonance imaging when employed concurrently. This allows magnetic resonance imaging monitoring of the heating associated with phototherapy.

Effect of the Dispersion Medium on NMR Relaxation Properties of Superparamagnetic Iron Oxide Nanoparticles between 0.24 mT and 14.1 T.

Due to weak exchange interactions, magnetite particles at a critical diameter of about 20 nm are considered monodomain. At this size, they exhibit a phenomenological magnetic property called superparamagnetism, making them useful as magnetic resonance imaging contrast agents, or MRI CAs. However, questions persist regarding the impact of using different physiological solvents and varying the environment in which these particles are dispersed on their performance, determined by their relaxivity. A colloidal suspension of superparamagnetic iron oxide nanoparticles (SPIONs) electrostatically stabilized by citrate ligand was synthesized using a fast, reliable, and reproducible developed microwave approach, ensuring high stability over time at pH 7. We studied the effects of three physiological media on these MRI CAs. Ultrapure water was used for the synthesis, while phosphate-buffered saline and physiological liquid were used to disperse the nanoparticles, as these media contain essential electrolytes for the functioning of the human body. The SPIONs underwent systematic characterizations to determine their physicochemical and magnetic properties. This study reports the longitudinal relaxivities of SPIONs at medically relevant magnetic field strengths. Field dependence of their relaxivity (efficacy) was evaluated using a nuclear magnetic resonance dispersion (NMRD) profile measured over a wide range of proton resonance frequencies between 5 kHz and 600 MHz. The Roch et al. model (Roch, A.; et al. J. Chem. Phys., 1999, 110, 5403-5411) was used to analyze the NMRD profile and evaluate the impact of SPIONs on water proton relaxation in the different redispersion media. It was observed in this study that the dynamics of water protons are not influenced by the redispersion media of these citrate-coated SPIONs. However, the presence of salt ions notably reduces their relaxivities by lowering the saturation magnetization of SPIONs.

Clustered ultra-small iron oxide nanoparticles as potential T1/T2 dual–modal magnetic resonance imaging contrast agents and application to tumor model

Many studies have been conducted on the use of ultra-small iron oxide nanoparticles (USIONs) (d < 3 nm) as potential positive magnetic resonance imaging (MRI)-contrast agents (CAs); however, there is dearth of research on clustered USIONs. In this study, nearly monodispersed clustered USIONs were synthesized using a simple two-step one-pot polyol method. First, USIONs (d = 2.7 nm) were synthesized, and clustered USIONs (d = 27.9 nm) were subsequently synthesized through multiple cross-linking of USIONs with poly(acrylic acid-co-maleic acid) (PAAMA) polymers with many -COOH groups. The clustered PAAMA-USIONs exhibited very weak ferromagnetism owing to the magnetic interaction between superparamagnetic USIONs; this was evidenced by their appreciable r1= 3.9 s‒1mM‒1and high r2/r1ratio of 14.6. Their ability to function as a dual-modal T1/T2MRI-CA in T1-weighted MRI was demonstrated when they simultaneously exhibited positive and negative contrasts in T1-weighted MRI of tumor model mice after intravenous injection. They displayed positive contrasts at the kidneys, bladder, heart, and aorta and negative contrasts at the liver and tumor.&#xD.

Algorithm development and metal oxide nanoparticle analysis in magnetic resonance imaging: Advancing neurodegenerative disease diagnostics

Magnetic resonance imaging (MRI) is critical in the diagnosis of neurodegenerative diseases, enabling the detection of brain lesions. Recent research has examined metallic nanoparticles (NPs) as MRI contrast agents (CAs) that can enhance lesion visibility by altering relaxation times. This study investigates the effects of metal oxide NPs on MRI relaxation times and brain lesion signals and proposes an algorithm for automated relaxation time determination using these NPs. The utilized NPs were synthesized using the sol‒gel method and characterized using Fourier-transform infrared spectroscopy and X-ray diffraction. MRI scans were performed on a phantom infused with varying concentrations of each metal oxide NP to assess changes in pixel signal intensities and relaxation rates. Our analysis involved segmenting the MRI images to focus on regions with different NP concentrations. The algorithm computed the longitudinal relaxation time for each region, revealing that Fe2O3 NPs exhibited the most substantial effect on signal intensity and relaxation time. The results indicated a high correlation (r = 0.9977), demonstrating strong agreement and confirming the reliability of our method. Our findings suggest that metallic oxide NPs, particularly Fe2O3, can considerably alter magnetization and act as effective negative CAs in MRI. These capabilities can improve the monitoring and treatment efficacy of neurodegenerative diseases. Our method for quantifying longitudinal relaxation times can potentially enhance routine clinical MRI assessments, offering a promising tool for future clinical applications.

Endotoxin Detection in Magnetic Resonance Imaging Contrast Agent Using Optimising Chromogenic Limulus Amebocyte Lysate Assay.

Endotoxin contamination in magnetic resonance imaging (MRI) contrast agents can pose a risk to patient safety causing immune reactions. Strict endotoxin limits are enforced for implants and catheters inserted into the body, but there are not clear rules for MRI contrast agents. Here, we investigated the efficacy of chromogenic LAL assay test for screening endotoxin activity in MRI contrast media manufactured in Malaysia. The powdered agent was dissolved in water for injection and endotoxin levels were measured. The coefficient of efficiency value for the standard curve, exhibiting r 2 ≥ 0.98, along with the absence of interfering substances and endotoxin activity below the regulatory threshold of 0.5 EU/mL, support the conclusion that the agent is unlikely to be pyrogenic or induce pyrogenic effect.

A Nitric Oxide-Sensing T1 Contrast Agent for In Vivo Molecular MR Imaging of Inflammatory Disease.

Nitric oxide (NO) is a signaling molecule that not only appears in the very early stage of inflammatory disease but also persists in chronic conditions. Its detection in vivo can, therefore, potentially enable early disease detection and treatment monitoring. Due to its transient nature and low abundance, however, noninvasive and deep-tissue imaging of NO dynamics is challenging. In this study, we present a magnetic resonance imaging (MRI) contrast agent based on a manganese porphyrin for specific imaging of NO. This agent is activated by NO, binds to tissue protein, accumulates so long as NO is actively produced, and confers a substantial bright contrast on T1-weighted MRI. In vitro tests confirm the specificity of activation by NO over other reactive oxygen or nitrogen species, absence of inflammation induced by the contrast agent, and sensitivity to NO levels in the tens of micromolar. In vivo demonstration in a mouse model of stress-induced acute myocardial inflammation revealed an over 2.2-times increase in T1 reduction in the inflamed heart compared to a healthy heart. This new NO-activatable T1 contrast agent holds the potential to provide early diagnosis of inflammatory disease, characterize different stages of inflammation, and ultimately guide the design of novel anti-inflammation therapeutics.

Construction of New MRI Contrast Agents for Spatiotemporal Visualization of Nitric Oxide in Ischemia/Reperfusion Organs.

Noninvasive and real-time nitric oxide (NO) visualization in vivo is still a challenge. Herein, we constructed a series of NO-responsive magnetic resonance imaging (MRI) contrast agents Gd1b-e by modifying Gd-DO3A using a bis-pyridyl-ethylamine side chain as a signal-amplifying moiety and o-phenylenediamine as a NO-responsive linker. It was found that Gd1b, d, and e can form macromolecular ternary complexes (Gd-Zn2+-HSA) with high longitudinal relaxivity (r1) (12.2-16.2 mM-1 s-1). Once reacting with NO, the o-phenylenediamine linker was hydrolyzed to produce a small molecular Gd complex with sharply decreased r1 (4.7-6.3 mM-1 s-1). Among them, Gd1d with a desirable pharmacokinetic profile (t1/2 = 5.91 h) could clearly distinguish the ischemia-reperfusion (IR) liver with excessive NO in rats. Meanwhile, the temporarily reduced amount of NO in the IR liver and brain by the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl could enhance the signal of Gd1d, suggesting anticipated NO-responsive property. This research offers a new avenue for insight into the NO spatiotemporal property in multiple IR organs.

Hydrogel Applications in the Diagnosis and Treatment of Glioblastoma.

Glioblastoma multiforme (GBM), a common malignant neurological tumor, has boundaries indistinguishable from those of normal tissue, making complete surgical removal ineffective. The blood-brain barrier (BBB) further impedes the efficacy of radiotherapy and chemotherapy, leading to suboptimal treatment outcomes and a heightened probability of recurrence. Hydrogels offer multiple advantages for GBM diagnosis and treatment, including overcoming the BBB for improved drug delivery, controlled drug release for long-term efficacy, and enhanced relaxation properties of magnetic resonance imaging (MRI) contrast agents. Hydrogels, with their excellent biocompatibility and customizability, can mimic the in vivo microenvironment, support tumor cell culture, enable drug screening, and facilitate the study of tumor invasion and metastasis. This paper reviews the classification of hydrogels and recent research for the diagnosis and treatment of GBM, including their applications as cell culture platforms and drugs including imaging contrast agents carriers. The mechanisms of drug release from hydrogels and methods to monitor the activity of hydrogel-loaded drugs are also discussed. This review is intended to facilitate a more comprehensive understanding of the current state of GBM research. It offers insights into the design of integrated hydrogel-based GBM diagnosis and treatment with the objective of achieving the desired therapeutic effect and improving the prognosis of GBM.

Micelles as nanocarriers of fluorescent and magnetic dendrimers for potential bimodal imaging applications

Bimodal magnetic-fluorescent materials that integrate magnetic and fluorescent properties have attracted significant attention due to their potential applications in biomedical imaging, biosensing, and therapeutic diagnosis. Tetra-amido-TEMPO 1, a compound that combines a fluorescent oligo(styryl)benzene dendrimer core with TEMPO radicals in its four branches was synthesized and used to form micelles with CTAB in water. DLS and Cryo-TEM techniques revealed the formation of micelles exhibiting a narrow particle size distribution, with an average hydrodynamic diameter ranging from 95 to 140 nm. After micellization, the ultraviolet-visible absorption and fluorescence emission intensities of micelles increased with tetra-amido-TEMPO concentration and EPR spectroscopy demonstrated consistent three-line spectra in the micelles, with the integrated area directly proportional to the amount of tetra-amido-TEMPO present. Besides, sufficient contrast enhancement in the proton T1 relaxation time-weighted magnetic resonance images in vitro proved their ability to act as magnetic resonance imaging (MRI) contrast agents. These tetra-amido-TEMPO/CTAB micelles offer an aqueous-compatible system for this bimodal fluorescent-magnetic molecule, showcasing proof of concept of their potential for biomedical applications.

Synergistic response of PEG coated manganese dioxide nanoparticles conjugated with doxorubicin for breast cancer treatment and MRI application

In this research work, we designed a smart biodegradable PEG-coated MnO2 nanoparticles conjugated with doxorubicin (PMnO2-Dox NPs) for dual chemo-photodynamic therapy and magnetic resonance imaging (MRI) application. This highly sensitive pH-responsive PMnO2-Dox NPs causes effective drug release under acidic pH environment. PMnO2-Dox NPs not only improves the efficacy of chemo-photodynamic therapy due to synergistic response as well as improved MRI imaging via boosting T1 MRI contrast. Manifold characterization techniques have been employed for materials investigation. Crystallography of PMnO2-Dox NPs were performed by using XRD analysis, which confirmed tetragonal crystal structure with an approximate crystallite size of 20–30 nm. Surface morphology was confirmed via SEM analysis, results indicated the spherical and asymmetric agglomerated nanocluster of PMnO2-Dox NPs. In in vitro bioassay, the anticancer activity of PMnO2-Dox NPs were tested against breast cancer (MCF-7) cell line using MTT test. Moreover, it can also inhibit the growth of primary and secondary cancers without light exposure. Results suggested that PMnO2-Dox NPs not only convenient for cancer treatment via combined chemo-photodynamic therapy but also address the way towards a comprehensive strategy for MRI application via bright contrast agent T1 after overcoming the problem of multidrug resistance (MDR) and synergistic response of therapeutic analysis.

Confounded Magnetic Resonance Imaging Contrast Agent Exposures and Gadolinium Retention in Organs

Confounded Magnetic Resonance Imaging Contrast Agent Exposures and Gadolinium Retention in Organs

Relaxivity Modulation of Gd-HPDO3A-like Complexes by Introducing Polar and Protic Peripheral Groups

In the last three decades, high-relaxivity Magnetic Resonance Imaging (MRI) contrast agents (CAs) have been intensively sought, aiming at a reduction in the clinically injected dose while maintaining the safety of the CA and obtaining the same pathological information. Thus, four new Gd(III) complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) macrocyclic structure were designed and synthesized by introducing further polar and protic functional groups (amides, phosphonates, and diols) adjacent to the metal-coordinated hydroxyl group. A detailed 1H NMR relaxometric analysis allowed us to investigate the effect of these functional groups on the relaxivity, which showed a 20–60% increase (at 0.5 T, 298 K, and pH 7.4) with respect to that of clinically approved CAs. The contribution of the water molecules H-bonded to these peripheral functional groups on the relaxivity was evaluated in terms of the second sphere effect or prototropic exchange of labile protons.

Advances in molecular imaging for early detection of lung cancer

Lung cancer remains the second most commonly diagnosed cancer globally and the leading cause of cancer-related deaths, a trend consistent in the United States as of 2023. One of the key reasons for the high mortality rate of lung cancer is its poor prognosis, with 75% of patients diagnosed at middle and advanced stages. Early detection of subclinical lung cancer, metastases, and their fibrotic stroma is crucial for enabling timely treatment, reducing reoccurrence, and stratifying patients. Current diagnostic methods, such as lung biopsy for patients with small nodules, are highly invasive and technically challenging. The radiological gold standard, computed tomography (CT), is associated with ionizing radiation. However, positron emission tomography (PET) and magnetic resonance imaging (MRI) have emerged as promising methodologies for lung cancer diagnosis. PET tracers with a variety of targeting mechanisms are currently under development in human trials. With advancements in hardware and software over the past decades, radiation-free MRI has been clinically and preclinically validated as an alternative to CT. Moreover, novel-targeted MRI contrast agents have been tested in animal models and show strong translational potential. In this review, we summarize the state-of-the-art progress in molecular imaging for the early detection of lung cancer and its potential biomarkers.

Optimized gadolinium-DO3A loading in RAFT-polymerized copolymers for superior MR imaging of aging blood-brain barrier.

The development of gadolinium-based contrast agents (GBCAs) has been pivotal in advancing magnetic resonance imaging (MRI), offering enhanced soft tissue contrast without ionizing radiation exposure. Despite their widespread clinical use, the need for improved GBCAs has led to innovations in ligand chemistry and polymer science. We report a novel approach using methacrylate-functionalized DO3A ligands to synthesize a series of copolymers through direct reversible addition-fragmentation chain transfer (RAFT) polymerization. This technique enables precise control over the gadolinium content within the polymers, circumventing the need for subsequent conjugation and purification steps, and facilitates the addition of other components such as targeting ligands. The resulting copolymers were analysed for their relaxivity properties, indicating that specific gadolinium-DO3A loading contents between 12-30 mole percent yield optimal MRI contrast enhancement. Inductively coupled plasma (ICP) measurements corroborated these findings, revealing a non-linear relationship between gadolinium content and relaxivity. Optimized copolymers were synthesized with the claudin-1 targeting peptide, C1C2, to image BBB targeting in aged mice to show imaging utility. This study presents a promising pathway for the development of more efficient GBCA addition to copolymers for targeted drug delivery and bioimaging application.

Theranostics: aptamer-assisted carbon nanotubes as MRI contrast and photothermal agent for breast cancer therapy

Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs’ ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable “theranostic alternatives” for breast cancer treatment.Graphical abstract