Dual-modal Contrast Agent Research Articles

Construction of CXCR4 Receptor-Targeted CuFeSe2 Nano Theranostic Platform and Its Application in MR/CT Dual Model Imaging and Photothermal Therapy.

Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need. We introduce an "all-in-one" tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region. CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM-1 s-1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo. CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential.

DNA-Mediated Magnetic-Dimer Assembly for Fault-Free Ultra-High-Field Magnetic Resonance Imaging of Tumors.

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.

Luciferase-Decorated Gold Nanorods as Dual-Modal Contrast Agents for Tumor-Targeted High-Performance Bioluminescence/Photoacoustic Imaging.

Gold nanorods (AuNRs) have been considered highly compelling materials for early cancer diagnosis and have aroused a burgeoning fascination among the biomedical sectors. By leveraging the versatile tunable optical properties of AuNRs, herein, we have developed a novel tumor-targeted dual-modal nanoprobe (FFA) that exhibits excellent bioluminescence and photoacoustic imaging performance for early tumor diagnosis. FFA has been synthesized by anchoring the recombinant bioluminescent firefly luciferase protein (Fluc) on the folate-conjugated AuNRs via the PEG linker. TEM images and UV-vis studies confirm the nanorod morphology and successful conjugation of the biomolecules to AuNRs. The nanoprobe FFA relies on the ability of the folate module to target the folate receptor-positive tumor cells actively, and simultaneously, the Fluc module facilitates excellent bioluminescent properties in physiological conditions. The success of chemical engineering in the present study enables stronger bioluminescent signals in the folate receptor-positive cells (Skov3, Hela, and MCF-7) than in folate receptor-negative cells (A549, 293T, MCF-10A, and HepG2). Additionally, the AuNRs induced strong photoacoustic conversion performance, enhancing the resolution of tumor imaging. No apparent toxicity was detected at the cellular and mouse tissue levels, manifesting the biocompatibility nature of the nanoprobe. Prompted by the positive merits of FFA, the in vivo animal studies were performed, and a notable enhancement was observed in the bioluminescent/photoacoustic intensity of the nanoprobe in the tumor region compared to that in the folate-blocking region. Therefore, this synergistic dual-modal bioluminescent and photoacoustic imaging platform holds great potential as a tumor-targeted contrast agent for early tumor diagnosis with high-performance imaging information.

Near-infrared Light-Triggered Size-Shrinkable theranostic nanomicelles for effective tumor targeting and regression

Most nanomedicines with suitable sizes (normally 100–200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) −triggered size-shrinkable micelle system (Fe3O4@AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe3O4@AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe3O4@AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe3O4@Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe3O4@AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to “visualize” the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe3O4@AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration.

Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy

BackgroundAs the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects.Methods and resultsIn this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination.ConclusionTumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Synthesis and characterization of cellulose nanocrystals/Gd2O3 nanocomposite as a dual-mode contrast agent for MRI via gamma-ray irradiation

This study developed a biocompatible nanocomposite using cellulose nanocrystals (CNCs), polyethylene glycol (PEG), and sodium hydroxide (NaOH), combined with gadolinium oxide nanoparticles (Gd2O3-NPs) through gamma radiation to decrease the size of nanoparticles and increase their uniformity. This research found that the (CNCs-PEG/NaOH)/Gd2O3 nanocomposite exhibits notable characteristics, including high saturation magnetization (1.44 emu/g), remarkable colloidal stability with a highly negative surface charge of −31.4 mV, and a small hydrodynamic size of 5.5 ± 0.7 nm. Furthermore, the MTT assay conducted on HeLa cell lines revealed the excellent biocompatibility of the (CNCs-PEG/NaOH)/Gd2O3 nanocomposite. No cytotoxic effects were observed, and the nanocomposite exhibited adequate cellular uptake. Moreover, the (CNCs-PEG/NaOH)/Gd2O3 nanocomposite displayed a remarkable enhancement effect on both T1 and T2-weighted images, with high r1 and r2 relaxivity values of 21.694 mM−1 s−1 and 43.799 mM−1 s−1, respectively, resulting in a relaxivity ratio (r2/r1) of 2.02 when compared to clinical and commercial agents. This biocompatible nanocomposite holds promise as a dual contrast agent in MRI and various other biomedical applications. It is envisaged that gamma irradiation is a good method to produce nanoparticles within the nanoscale range.

Design of magnetic nanoplatforms for simultaneous molecular imaging and cisplatin delivery for breast cancer cells theranostics

Developing intelligent nanomedicines for cancer diagnosis and treatment (theranostics) is pivotal for improving treatment outcomes. In this study, we synthesized and evaluated dual-mode MRI contrast agents utilizing superparamagnetic iron oxide nanoparticles (SPIONs) as the core and samarium ions as the coating. Samarium ions were grafted onto the polymeric coating layer of the nanoparticles via electrostatic deposition. Characterization of the Cis/Fe3O4/PEG-co-PMMA/SmO2 core/shell structures involved size, morphology, drug loading, encapsulation efficiency, and their potential as T1-T2 dual-model contrast agents. Longitudinal relaxivity (r1) and transverse relaxivity (r2) were estimated using NMR relaxation times. In vivo investigations assessed the effectiveness of Cisplatin, particularly in human breast cancer (MCF-7) cells, using wound healing assays and molecular analysis. Remarkably, the Cis/Fe3O4/PEG-co-PMMA/SmO2 formulation exhibited enhanced cytotoxicity against MCF-7 cells compared to Cisplatin alone, indicating its promising role as an inhibitory agent against breast cancer cell proliferation.

Rational Design of Magnetic Nanoparticles as T1-T2 Dual-Mode MRI Contrast Agents.

Magnetic nanoparticles (MNPs), either paramagnetic or superparamagnetic depending on their composition and size, have been thoroughly studied as magnetic resonance imaging (MRI) contrast agents using in vitro and in vivo biomedical preclinical studies, while some are clinically used. Their magnetic properties responsible in some cases for high magnetization values, together with large surface area-to-volume ratios and the possibility of surface functionalization, have been used in MRI-based diagnostic and theranostics applications. MNPs are usually used as positive (T1) or negative (T2) MRI contrast agents, causing brightening or darkening of selected regions in MRI images, respectively. This review focusses on recent developments and optimization of MNPs containing Gd, Mn, Fe and other lanthanide ions which may function as dual-mode T1-T2 MRI contrast agents (DMCAs). They induce positive or negative contrast in the same MRI scanner upon changing its operational mode between T1-weighted and T2-weighted pulse sequences. The type of contrast they induce depends critically on their r2/r1 relaxivity ratio, which for DMCAs should be in the 2-10 range of values. After briefly discussing the basic principles of paramagnetic relaxation in MNPs, in this review, the basic strategies for the rational design of DMCAs are presented and typical examples are discussed, including in vivo preclinical applications: (1) the use of NPs with a single type of contrast material, Gd- or Mn-based NPs or superparamagnetic NPs with appropriate size and magnetization to provide T2 and T1 contrast; and (2) inclusion of both types of T1 and T2 contrast materials in the same nanoplatform by changing their relative positions.

Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions.

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανβ3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.

A NIR-II Photoacoustic/NIR-IIa Fluorescent Probe for Targeted Imaging of Glioma under NIR-II Excitation.

Fluorescence and photoacoustic (PA) imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has garnered massive interest owing to high maximum permissible exposure of light, reduced autofluorescence, and improved deep penetration. However, active targeted NIR-II photoacoustic/NIR-IIa fluorescence imaging of glioma under NIR-II excitation has been seldom reported, which is partly ascribable to the lack of suitable materials. In this study, a small-molecule-based αvβ3-targeted NIR-II photoacoustic/NIR-IIa fluorescent probe IR-32p was generated and subsequently evaluated in U87MG tumor-bearing mice excited with NIR-I and NIR-II light. Exceptional dual-modal imaging properties such as good tumor uptake, high targeting specificity, and high tumor contrast were achieved in an orthotopic glioma model under 1020/1064 nm excitation, exhibiting a superior imaging depth of glioma through the skull. Our study introduces an outstanding dual-modal contrast agent with NIR-II absorption and confirms the superiority of NIR-II excitation over NIR-I in in vivo NIR-II/PA imaging.

Gamma-Camera Direct Imaging of the Plasma and On/Intra Cellular Distribution of the 99mTc-DPD-Fe3O4 Dual-Modality Contrast Agent in Peripheral Human Blood.

The radiolabeled iron oxide nanoparticles constitute an attractive choice to be used as dual-modality contrast agents (DMCAs) in nuclear medical diagnosis, due to their ability to combine the benefits of two imaging modalities, for instance single photon emission computed tomography (SPECT) with magnetic resonance imaging (MRI). Before the use of any DMCA, the investigation of its plasma extra- and on/intra cellular distribution in peripheral human blood is of paramount importance. Here, we focus on the in vitro investigation of the distribution of 99mTc-DPD-Fe3O4 DMCA in donated peripheral human blood (the ligand 2-3-dicarboxypropane-1-1-diphosphonic-acid is denoted as DPD). Initially, we described the experimental methods we performed for the radiosynthesis of the 99mTc-DPD-Fe3O4, the preparation of whole blood and blood plasma samples, and their incubation conditions with 99mTc-DPD-Fe3O4. More importantly, we employed a gamma-camera apparatus for the direct imaging of the 99mTc-DPD-Fe3O4-loaded whole blood and blood plasma samples when subjected to specialized centrifugation protocols. The direct comparison of the gamma-camera data obtained at the exact same samples before and after their centrifugation enabled us to clearly identify the distribution of the 99mTc-DPD-Fe3O4 in the two components, plasma and cells, of peripheral human blood.

Canine preclinical safety evaluation of a multimodal nanoparticle agent (Nanotrast-CF800) for image-guided cancer surgery.

Surgical oncology often requires the use of contrast-enhanced cross-sectional imaging preoperatively to characterize solitary tumours and identify sentinel lymph nodes. Intraoperative optical guidance can effectively aid tissue-sparing tumour excision and locate sentinel lymph nodes. Nanotrast-CF800 (CF800) is a novel dual-modality contrast agent, which co-encapsulates iohexol and indocyanine green (ICG) within a liposomal nanoparticle. It was developed for preoperative and intraoperative imaging of solitary tumours and sentinel lymph node mapping and its efficacy has been demonstrated in preclinical animal models (Zheng et al. 2015). The objective of this study is to evaluate the safety profile of CF800 following intravenous administration in healthy dogs. Six research dogs were randomized into two groups. Group 1 received a low dose (1 mL/kg) and group 2 received a high dose (5 mL/kg). Dogs were placed under general anesthesia and a continuous rate infusion of CF800 was administered based on group allocation. Physiologic parameters including heart rate, respiratory rate, direct arterial blood pressure, cardiac output, and temperature were measured at set time points. Plasma concentrations of iohexol, ICG, and histamine were measured at set time points. Dogs underwent whole body computed tomography scans pre-injection, 2-, and 7-days post-injection (p.i.). Contrast enhancement was measured in select organ systems and great vessels at each time point. There were no significant changes in physiologic parameters following IV infusion of CF800 in all dogs. Plasma iohexol and ICG concentrations peaked at 1 day p.i., while histamine concentrations peaked at 30 minutes p.i. Significant contrast enhancement was noted within the liver, heart, aorta, and caudal vena cava on day 2 p.i., which was significantly different compared to baseline. Prolonged contrast retention within the liver was identified. Intravenous administration of CF800 was safe to use in healthy dogs with no significant systemic adverse effects.

A polymeric 1H/19F dual-modal MRI contrast agent with a snowman-like Janus nanostructure.

Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinics, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with a T2 relaxation time of 5 ms and an r1 value of 0.31 mM-1 s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.

Folic Acid-Conjugated Fe-Au-Based Nanoparticles for Dual Detection of Breast Cancer Cells by Magnetic Resonance Imaging and Computed Tomography

Purpose: We synthesized folic acid-conjugated Fe3O4/Au-pralidoxime chloride Nanoparticles (Fe2O3/Au@PAM NPs) for use as dual-modal contrast agents for Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) in the diagnosis of breast cancer.
 Materials and Methods: Fe2O3/Au@PAM NPs labeled or not to folic acid were synthesized and analyzed by dynamic light scattering, transmission electron microscopy, and vibrating sample magnetometry. The ability of these NPs to create image contrast was also investigated in silico and in vitro (in MCF-7 breast cancer cells and A549 lung cancer cells) with CT and MRI.
 Results: Dynamic light scattering and transmission electron microscopy revealed that the Fe2O3/Au@PAM NPs were nearly spherical. The average diameter of Fe2O3/Au NPs increased from 11.6 nm to 98 nm after folic acid conjugation. The saturation magnetization values of Fe2O3/Au@PAM NPs with and without folic acid conjugation were 25.56 and 32.6 emu/g, respectively. Conjugation of folic acid to NPs greatly improved their uptake by cancer cells. The additional coating of NPs with FA reduced the T2 relaxation time and signal intensity for MRI. Folic acid-labeled MCF-7 cells had a radiodensity measurement of 208 Hunsfield Units (HU) compared to 95 HU for A549 cells. For breast cancer cells, NPs labeled with folic acid significantly improved the X-ray absorption coefficient as a sign of active cellular uptake compared to NPs without labeling.
 Conclusion: Folic acid-labeled Fe2O3/Au@PAM NPs can serve as dual CT/MRI contrast agents and improve the sensitivities of both modalities for the detection of cancer cells.

Chelating ligand-bridged IO-Gd nanoparticles with enhanced contrast performance for dual-mode MRI

Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique that has been widely applied in the clinical diagnosis of diseases across various fields. Currently, there is a dearth of high-performance dual-mode contrast agents that provide precise diagnostic information for complex diseases. In this study, iron oxide-gadolinium nanoparticles (IO-Gd NPs) bridged by hydrophilic ligand ethylenediamine tetramethylenephosphonic acid (EDTMP) are designed inspired by Solomon-Bloembergen–Morgan (SBM) theory, where T1 and T2 relaxivity increase with a reduction in Gd content. In particular, the NPs with minimum Gd content exhibit excellent dual-mode contrast performance (r1 = 94.42 mM−1 s−1, r2 = 343.62 mM−1 s−1). The underlying mechanism is that the bridged EDTMP coordinate limits Gd tumbling and forces Gd3+ to expose itself to the surface of the NPs. This provides more opportunities for water molecules to coordinate with Gd3+ and significantly enhances proton relaxivity. Moreover, the hydrophilicity of the ligand enhances the water dispersion stability of the NPs and increases the exchange rate of water protons near the NPs, further enhancing the dual-mode contrast effect. Finally, the biocompatibility and in vitro/vivo imaging performances of the IO@EDTMP-Gd NPs are systematically evaluated, and the results demonstrate their potential as dual-mode contrast agents. This study provides a new strategy for developing dual-mode MRI contrast agents that can further improve the accuracy of MRI in the diagnosis of complex diseases.

Tannic acid-mediated synthesis of flower-like mesoporous MnO2 nanostructures as T1–T2 dual-modal MRI contrast agents and dual-enzyme mimetic agents

This study introduces a simple method for preparing a new generation of MnO2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO2 NMs, flower-like M1-MnO2 and near-spherical M2-MnO2, were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (Ms), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO2. Furthermore, the signal intensity and r1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T1 MRI contrast activities could be employed as a promising theranostic system for future purposes.

Graphene Quantum Dots for Multifaceted Diagnostics

Due to their unique physical and electronic properties as well as high biocompatibility and water solubility, functionalized graphene quantum dots (GQDs) have found utilization in a variety of biomedical applications. GQDs can serve as carriers for drugs and genes while tracing their delivery pathways in vitro and in vivo with their visible and near-infrared fluorescence. In addition to therapeutic applications, our recent work explores diagnostic modalities of these novel nanomaterials. GQDs synthesized bottom-up form a single glucosamine precursor, or top-down from reduced graphene oxide can serve as nanoscale temperature sensors for biological processes. They exhibit linear and reversible visible/NIR fluorescence quenching by up to 19.3 % in suspension with temperature increase form 25 to 49 ⁰C. A more pronounced trend is observed in HeLa cells with over 40% quenching in that temperature range. Our findings suggest that such deterministic response can serve as non-invasive reversible/photostable mechanism for temperature sensing in microscopic subcellular biological environments. Another diagnostic modality of GQDs involves their capability for magnetic resonance imaging. When doped with Mn2+ ions during their bottom-up synthesis, GQDs exhibit substantial r₂/r₁ relaxation parameter ratios of 11.19, showing potential as dual-mode T1 or T2 contrast agents. Their Gd3+-doped counterparts possess r₂/r₁ ratios of 1.148 with high r1 of 9.546 mM-1s-1 compared to commercial contrast agents, suggesting their utilization as T1 contrast agents. Given that doping did not affect their biocompatibility or fluorescence properties, such doped GQDs can serve as multimodal MR and fluorescence imaging agents. Metal-doped GQDs possess the capability ultrasonic contrast imaging that can be utilized for higher precision and deeper tissue diagnostic applications. They demonstrate high-contrast properties in ultrasound brightness mode by a factor of 10 surpassing undoped GQD structures. The successful imaging enhancement was observed in tissue phantom and animal tissue, suggesting that GQDs can be tracked by ultrasound imaging and used as contrast agents for the improvement of the deterministic power of this widely available imaging approach. GQD intrinsic fluorescence can itself serve as a non-invasive diagnostic sensing tool, as it can be affected by the binding of different drugs, genes and biomolecules to the GQDs. This optical sensing mechanism is used in our work for identifying trace quantities of cancer-generated genes for early personalized cancer detection. The sensor is prepared from GQDs complexed with the bait DNA sequence complementary to the target pancreatic cancer miRNA. It effectively discriminates between complementary single-stranded DNA sequences and random control genes with the sensitivity in the nanomolar range. Cancer gene detection is further verified by identifying both, the stem and the loop portions of the pancreatic cancer-generated pre-miR-132. Given the success of these different diagnostic applications, GQDs can be considered a highly perspective theragnostic tool for a variety of disease targets.

Manganese-Doped Carbon Dots as a Promising Nanoprobe for Luminescent and Magnetic Resonance Imaging

Luminescent carbon nanodots (CDs) are a low-toxic nanomaterial with a tunable emission in a wide spectral range and with various functional groups on the surface. Therefore, CDs can prospectively serve as luminescent nanoprobes for biomedical applications, such as drug-delivery, visualization, sensing, etc. The doping of CDs with paramagnetic or transition metals allows the expansion of the range of applications of CDs and the fabrication of a multimodal nanoprobe for bioimaging. Here, we developed CDs doped with manganese (Mn) based on commonly used precursors—o-phenylenediamine or citric acid and formamide. The chemical structure, morphology, optical properties, and magnetic resonance responses have been carefully studied. The obtained CDs are up to 10 nm, with emissions observed in the 400–650 nm spectral region. CDs exhibit an ability to reduce both T1 and T2 relaxation times by up to 6.4% and 42.3%, respectively. The high relaxivity values suggest the use of CDs as promising dual-mode contrast agents for T1 and T2 MRI. Therefore, our developed CDs can be utilized as a new multifunctional nanoscale probe for photoluminescent and magnetic resonance bioimaging.

Exploring multi-element co-doped carbon dots as dual-mode probes for fluorescence/CT imaging

Osteosarcoma (OS), the most common pediatric malignant bone tumor, has been stagnant in its current treatment status due to its highly heterogeneous, aggressive, and lethal nature. Herein, we developed multi-element charge-transfer co-doped carbon dots (CDs) as dual-mode contrast agents for OS models using hydrothermal carbonization. The obtained P, W co-doped CDs, P, W, Hf co-doped CDs-1, and P, W, Hf co-doped CDs-2 have high long-wavelength quantum yields (16.5, 27.3, and 14.2%) in N, N-dimethylformamide solution, which can be attributed to the presence of valence electrons in the doped metal ions or metal hydrochloride, which promotes the radiative recombination of electrons and the formation of holes. Moreover, P, W, Hf co-doped CDs-1 exhibited higher biocompatibility, good 143B cell imaging, and fluorescence/CT high contrast imaging performance in Balb/C tumor-bearing mice compared to P, W co-doped CDs, and P, W, Hf co-doped CDs-2. In addition, the biodistribution and pharmacokinetic results further indicate that P, W, Hf co-doped CDs-1 has apparent advantages in imaging tracking and biosafety of OS and has excellent potential as a dual-mode imaging contrast agent.

Magnetic Nanoparticle-Based High-Performance Positive and Negative Magnetic Resonance Imaging Contrast Agents.

In recent decades, magnetic nanoparticles (MNPs) have attracted considerable research interest as versatile substances for various biomedical applications, particularly as contrast agents in magnetic resonance imaging (MRI). Depending on their composition and particle size, most MNPs are either paramagnetic or superparamagnetic. The unique, advanced magnetic properties of MNPs, such as appreciable paramagnetic or strong superparamagnetic moments at room temperature, along with their large surface area, easy surface functionalization, and the ability to offer stronger contrast enhancements in MRI, make them superior to molecular MRI contrast agents. As a result, MNPs are promising candidates for various diagnostic and therapeutic applications. They can function as either positive (T1) or negative (T2) MRI contrast agents, producing brighter or darker MR images, respectively. In addition, they can function as dual-modal T1 and T2 MRI contrast agents, producing either brighter or darker MR images, depending on the operational mode. It is essential that the MNPs are grafted with hydrophilic and biocompatible ligands to maintain their nontoxicity and colloidal stability in aqueous media. The colloidal stability of MNPs is critical in order to achieve a high-performance MRI function. Most of the MNP-based MRI contrast agents reported in the literature are still in the developmental stage. With continuous progress being made in the detailed scientific research on them, their use in clinical settings may be realized in the future. In this study, we present an overview of the recent developments in the various types of MNP-based MRI contrast agents and their in vivo applications.