High Transverse Relaxivity Research Articles

Gas phase synthesis of core-shell Fe@FeO x magnetic nanoparticles into fluids

Sorbitol, short chain molecules, have been used to stabilise of Fe@FeOx nanoparticles produced in the gas phase under the ultra-high vacuum (UHV) conditions. The sorbitol coated Fe@FeOx nanoparticles produced by our method have a narrow size distribution with a hydrodynamic diameter of 35 nm after NaOH is added to the solution. Magnetisation measurement shows that the magnetic nanoparticles are superparamagnetic at 100 K and demonstrate hysteresis at 5 K with an anisotropy constant of 5.31 × 104 J/m3 (similar to bulk iron). Also, it is shown that sorbitol is only suitable for stabilising the Fe@FeOx suspensions, and it does not prevent further oxidation of the metallic Fe core. According to MRI measurement, the nanoparticles have a high transverse relaxation rate of 425 mM−1 s−1.

Direct one-pot synthesis of glutathione capped hydrophilic FePt-CdS nanoprobe for efficient bimodal imaging application

One-pot synthesis methods for development of hydrophilic imaging nanoprobes have advantages over multi-pot methods due to their simple procedures, less probability for degradation of efficiency, superior control over growth and morphology, cost effectiveness, improved scope for scale-up synthesis etc. Here, we present a novel one-pot facile synthesis of hydrophilic colloidal bimodal nanoprobe (FePt-CdS) prepared through a seed-mediated nucleation and growth technique. In this facile synthesis of complex nanostructure, glutathione (GSH) was used as the capping agent to render biocompatibility and dispersibility. The microstructure, surface, optical, magnetic, biocompatibility, relaxivity and imaging property of the developed nanoprobe have been studied. The microstructural characterizations reveal average size of the particle as ~9–11nm with bleb shaped morphology. Spectroscopic characterization depicts the development of GSH capped CdS QDs on FePt, surface functionalities and their stability. The magnetic measurements confirm the superparamagnetic property in the developed bimodal nanoprobe. In addition, the GSH capping imparts excellent biocompatibility, water dispersibility, and fluorescence property to the probe. In RAW 264.7 macrophage cells, the bimodal nanoprobes exhibit intense green and red fluorescence. The magnetic resonance imaging (MRI) and fluorescence imaging (FI) study depict high transverse relaxivity and visible range fluorescent property in the synthesized FePt-CdS nanoprobe. Hence, the developed bimodal nanoprobe can be used as a potential candidate in simultaneous FI and MR imaging.

Preparation of Mn-Zn ferrite nanoparticles and their silica-coated clusters: Magnetic properties and transverse relaxivity

Hydrothermal synthesis of Mn1−xZnxFe2O4 nanoparticles followed by direct encapsulation of the as-grown material into silica is demonstrated as a fast and facile method for preparation of efficient negative contrast agents based on clusters of ferrite crystallites. At first, the hydrothermal procedure is optimized to achieve strictly single-phase magnetic nanoparticles of Mn-Zn ferrites in the compositional range of x≈0.2–0.6 and with the mean size of crystallites ≈10nm. The products are characterized by powder X-ray diffraction, X-ray fluorescence spectroscopy, and SQUID magnetometry, and the composition close to x=0.4 is selected for the preparation of silica-coated clusters with the mean diameter of magnetic cores ≈25nm. Their composite structure is studied by means of transmission electron microscopy combined with detailed image analysis and magnetic measurements in DC fields. The relaxometric studies, performed in the magnetic field of B0=0.5T, reveal high transverse relaxivity (r2(20°C)=450s−1mmol(Me3O4)−1L) with a pronounced temperature dependence, which correlates with the observed temperature dependence of magnetization and is ascribed to a mechanism of transverse relaxation similar to the motional averaging regime.

Antioxidative Theranostic Iron Oxide Nanoparticles toward Brain Tumors Imaging and ROS Production

Gliomas are the most common primary brain tumor in humans. To date, the only treatment of care consists of surgical removal of the tumor bulk, irradiation, and chemotherapy, finally resulting in a very poor prognosis due to the lack of efficiency in diagnostics. In this context, nanomedicine combining both diagnostic and magnetic resonance imaging (MRI) and therapeutic applications is a relevant strategy referred to theranostic. Magnetic nanoparticles (NP) are excellent MRI contrast agents because of their large magnetic moment, which induces high transverse relaxivity (r2) characteristic and increased susceptibility effect (T2*). NP can be also used for drug delivery by coating their surface with therapeutic molecules. Preliminary in vitro studies show the high potential of caffeic acid (CA), a natural polyphenol, as a promising anticancer drug due to its antioxidant, anti-inflammatory, and antimetastatic properties. In this study, the antioxidative properties of iron oxide NP functionalized with caffeic acid (γFe2O3@CA NP) are investigated in vitro on U87-MG brain cancer cell lines. After intravenous injection of these NP in mice bearing a U87 glioblastoma, a negative contrast enhancement was specifically observed on 11.7 T MRI images in cancerous tissue, demonstrating a passive targeting of the tumor with these nanoplatforms.

Targeted Superparamagnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging of T-Cells in Rheumatoid Arthritis.

The purpose of the study is to develop a targeted nanoparticle platform for T cell labeling and tracking in vivo. Through carboxylation of the polyethylene glycol (PEG) surface of SPION, carboxylated-PEG-SPION (IOPC) was generated as a precursor for further conjugation with the targeting probe. The IOPC could readily cross-link with a variety of amide-containing molecules by exploiting the reaction between 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide and N-hydroxysuccinimide. The subsequent conjugation of monoclonal anti-CD3 antibody with IOPC made it possible to construct a magnetic resonance imaging (MRI) contrast agente (CA) that targets T cells, named IOPC-CD3. IOPC-CD3 was found to have high transverse relaxivity, good targeting selectivity, and good safety profile in vitro. The utility of this newly synthesized CA was explored in an in vivo rodent collagen-induced arthritis (CIA) model of rheumatoid arthritis. Serial MRI experiments revealed a selective decrease in the signal-to-noise ratio of the femoral growth plates of CIA rats infused with IOPC-CD3, with this finding being consistent with immunohistochemical results showing the accumulation of T cells and iron oxide nanoparticles in the corresponding region. Together with the abovementioned desirable features, these results indicate that IOPC-CD3 offers a promising prospect for a wide range of cellular and molecular MRI applications.

In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody.

The feasibility of iron oxide nanoparticles (IONPs) conjugated with anti-epidermal growth factor receptor 2 (HER2) single-chain antibody (scFv-IONPs) as novel HER2-targeted magnetic resonance (MR) contrast agents was investigated. The scFv-IONPs were prepared and identified. For in vitro MRI, NCI-N87 (HER2 high expression) and SUIT2 (low expression) cells were incubated with scFv-IONPs. For in vivo MRI, NCI-N87 and SUIT2 tumor-bearing mice were intravenously injected with scFv-IONPs and imaged before and 24h post-injection. The scFv-IONPs demonstrated high transverse relaxivity (296.3s-1mM-1) and affinity toward HER2 (KD = 11.7nM). In the in vitro MRI, NCI-N87 cells treated with scFv-IONPs exhibited significant MR signal reduction (44.6%) than SUIT2 cells (6.8%). In the in vivo MRI, decrease of MR signals in NCI-N87 tumors (19.3%) was more notable than that in SUIT2 tumors (6.2%). The scFv-IONPs enabled HER2-specific tumor MR imaging, suggesting the potential of scFv-IONPs as a robust HER2-targeted MR contrast agent.

915 nm Light‐Triggered Photodynamic Therapy and MR/CT Dual‐Modal Imaging of Tumor Based on the Nonstoichiometric Na0.52YbF3.52:Er Upconversion Nanoprobes

Lanthanide (Ln(3+) )-doped upconversion nanoparticles (UCNPs) as a new generation of multimodal bioprobes have attracted great interest for theranostic purpose. Herein, red emitting nonstoichiometric Na0.52 YbF3.52 :Er UCNPs of high luminescence intensity and color purity are synthesized via a facile solvothermal method. The red UC emission from the present nanophosphors is three times more intense than the well-known green emission from the ≈30 nm sized hexagonal-phase NaYF4 :Yb,Er UCNPs. By utilizing Na0.52 YbF3.52 :Er@SrF2 UCNPs as multifunctional nanoplatforms, highly efficient in vitro and in vivo 915 nm light-triggered photodynamic therapies are realized for the first time, with dramatically diminished overheating yet similar therapeutic effects in comparison to those triggered by 980 nm light. Moreover, by virtue of the high transverse relaxivity (r 2 ) and the strong X-ray attenuation ability of Yb(3+) ions, these UCNPs also demonstrate good performances as contrast agents for high contrast magnetic resonance and X-ray computed tomography dual-modal imaging. Our research shows the great potential of the red emitting Na0.52 YbF3.52 :Er UCNPs for multimodal imaging-guided photodynamic therapy of tumors.

Increased transverse relaxivity in ultrasmall superparamagnetic iron oxide nanoparticles used as MRI contrast agent for biomedical imaging.

Synthesis of a contrast agent for biomedical imaging is of great interest where magnetic nanoparticles are concerned, because of the strong influence of particle size on transverse relaxivity. In the present study, biocompatible magnetic iron oxide nanoparticles were synthesized by co-precipitation of Fe2+ and Fe3+ salts, followed by surface adsorption with reduced dextran. The synthesized nanoparticles were spherical in shape, and 12 ± 2 nm in size as measured using transmission electron microscopy; this was corroborated with results from X-ray diffraction and dynamic light scattering studies. The nanoparticles exhibited superparamagnetic behavior, superior T2 relaxation rate and high relaxivities (r1 = 18.4 ± 0.3, r2 = 90.5 ± 0.8 s-1 mM-1 , at 7 T). MR image analysis of animals before and after magnetic nanoparticle administration revealed that the signal intensity of tumor imaging, specific organ imaging and whole body imaging can be clearly distinguished, due to the strong relaxation properties of these nanoparticles. Very low concentrations (3.0 mg Fe/kg body weight) of iron oxides are sufficient for early detection of tumors, and also have a clear distinction in pre- and post-enhancement of contrast in organs and body imaging. Many investigators have demonstrated high relaxivities of magnetic nanoparticles at superparamagnetic iron oxide level above 50 nm, but this investigation presents a satisfactory, ultrasmall, superparamagnetic and high transverse relaxivity negative contrast agent for diagnosis in pre-clinical studies. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of Water Exchange Kinetics on [Ln(AAZTAPh-NO2)(H2O)q](x) Complexes Using Proton Nuclear Magnetic Resonance.

Water exchange kinetics on [Ln(AAZTAPh-NO2)(H2O)q](-) (Ln = Gd(3+), Dy(3+), or Tm(3+)) were determined by (1)H nuclear magnetic resonance (NMR) measurements. The number of inner-sphere water molecules was found to change from two to one when going from Dy(3+) to Tm(3+). The calculated water exchange rate constants obtained by variable-temperature proton transverse relaxation rates are 3.9 × 10(6), 0.46 × 10(6), and 0.014 × 10(6) s(-1) at 298 K for Gd(3+), Dy(3+), and Tm(3+), respectively. Variable-pressure measurements were used to assess the water exchange mechanism. The results indicate an associative and dissociative interchange mechanism for Gd(3+) and Dy(3+) complexes with ΔV(⧧) values of -1.4 and 1.9 cm(3) mol(-1), respectively. An associative activation mode (Ia or A mechanism) was obtained for the Tm(3+) complex (ΔV(⧧) = -5.6 cm(3) mol(-1)). Moreover, [Dy(AAZTAPh-NO2)(H2O)2](-) with a very high transverse relaxivity value was found as a potential candidate for negative contrast agents for high-field imaging applications.

One-step continuous synthesis of functionalized magnetite nanoflowers

For the first time, functionalized magnetite nanoparticles (Fe3O4 NPs) that form aggregates with a nanoflower morphology were synthesized using a rapid (11 s) one-step continuous hydrothermal process, which was recently modified, and their application as a T2 magnetic resonance imaging (MRI) contrast agent was evaluated. The nanoparticles functionalized with 3,4-dihydroxy-L-phenylalanine (LDOPA) or 3,4-dihydroxyhydrocinnamic acid (DHCA) consisted of small crystallites of approximately 15 nm of diameter that assembled to form flower-shaped aggregate structures. The Fe3O4–LDOPA nanoflowers exhibited a high transverse relaxivity, r2 of 418 ± 10 l mmolFe−1 s−1 at 3 T owing to magnetic dipolar interactions, which is twice as that of the commercial Feridex®/Endorem®. The prepared nanostructures were compared with bare Fe3O4 NPs and citrated Fe3O4 NPs. DHCA, LDOPA, and citric acid (CA) were found to have an anti-oxidizing effect and to influence the crystallite size and the lattice parameter of the NPs. DHCA and LDOPA increased the crystallite size, whereas CA decreased it. Surface modification increased the colloidal stability of NPs as compared to bare NPs. Nanoflower suspensions of Fe3O4–LDOPA NPs were found to be stable in the phosphate-buffered saline, saline medium, and minimal essential medium and formed aggregates of sizes smaller than 120 nm. All samples were found to be superparamagnetic in nature and the highest saturation magnetization was obtained for the Fe3O4–LDOPA samples. These NPs can bind to polymers such as PEG, and to fluorescent and chelating agents owing to the presence of free –NH2 or –COOH groups on the surface of NPs, allowing their use in dual imaging applications.

Functionalized magnetic nanochains with enhanced MR imaging: A novel nanosystem for targeting and inhibition of early glioma

Absence of efficient targeting limits the application of magnetic nanochains (NCs) in the diagnosis of early brain cancer. Herein, dextran-coated NCs (more than 100nm length and ∼10nm cores diameter), which were modified by cyclic pentapeptide c(RGDyC) or chlorotoxin (CTX) as the targeting molecules, were fabricated via carbodiimide chemistry and thiol technique. The analysis results revealed that the obtained slender NCs exhibited good biocompatibility, superparamagnetic property, high transverse relaxivity (R2) and longer blood circulation time. The test results of human umbilical vein endothelial cells and U251 human glioma cells indicated that the conjugation of c(RGDyC) could obviously increase the cyto-internalization of c(RGDyC)-NCs, however, CTX modification could significantly enhance accumulation of CTX-NCs in U251 cells, leading to cellular apoptosis. The results of in vivo biodistribution tests and in vivo magnetic resonance (MR) imaging indicated that, although the c(RGDyC)-NCs could target early glioma to some extent and obviously enhance the contrast of MR imaging, CTX-NCs possessed higher tumor-targeting ability and good inhibition effect than the c(RGDyC)-NCs, suggesting that CTX-NCs are promising candidates for the diagnosis and therapy of early glioma.

Multifunctional β-NaGdF4:Ln3+ (Ln = Yb, Er, Dy) nanoparticles with NIR to visible upconversion and high transverse relaxivity: a potential bimodal contrast agent for high-field MRI and optical imaging

Developed nano β-NaGdF4 doped with Yb3+/Er3+ in the core and Yb3+/Dy3+ in the shell with favorable properties for combined magnetic resonance and optical imaging.

Polydopamine-based coordination nanocomplex for T1/T2 dual mode magnetic resonance imaging-guided chemo-photothermal synergistic therapy

Despite the progress in the design and synthesis of theranostic agents, limitations on efficiency and safety offer significant room for improvement in these agents. Inspired by the natural binding ability of polydopamine nanospheres (PDAs) with iron ion, a simple and versatile synthesis strategy is developed to prepare biodegradable coordination polymer (CP) encapsulated PDAs nanocomplex (PDAs@CPx, x = 3, 6, 9). We found that the PDAs@CP3 can serve as a T1/T2 dual mode contrast agent (DMCA) for magnetic resonance imaging (MRI), which possesses high longitudinal (r1 = 7.524 mM−1 s−1) and transverse (r2 = 45.92 mM−1 s−1) relaxivities. In this system, benefitting from the high photothermal conversion efficiency derived from PDAs, DOX loaded PDAs@CP3 nanocomplex is able to not only destroy the tumor directly by heat, but also stimulate the chemotherapy by enabling NIR-responsive on demand delivery of DOX. To the best of our knowledge, this is the first example exploring the potential of PDAs@CPx nanocomplex for T1/T2 dual mode MRI-guided chemo-photothermal synergistic therapy. This work extends the currently available theranostic agents, and opens up new avenues to rationally design the high-performance T1/T2 DMCA.

Improved Transversal Relaxivity for Highly Crystalline Nanoparticles of Pure γ‐Fe2O3 Phase

Pure and highly crystalline γ-Fe2O3 nanocrystals (NCs) are obtained when hydrolysis and oxidation of a Fe(II) organometallic precursor are performed in successive steps. Their synthesis in pure alkylamine leads to NCs of about 6 nm. In aqueous solutions of poly(vinyl)pyrrolidone, such pristine NCs form aggregates of about 150 nm that exhibit a high transversal relaxivity (r2 =466 mM(-1) s(-1)) about four times higher than that of a commercial Feridex magnetic resonance imaging (MRI) contrast agent. Consequently, they provide a significant decrease in the NMR signal at very short echo time (8 ms), which is of paramount importance in clinical practice because of the reduced duration of MRI measurements.

Core–shell superparamagnetic nanoparticles with interesting properties as contrast agents for MRI

Core–shell nanoparticles (NPs) formed by superparamagnetic iron oxide NPs (SPIONs) coated with inorganic or organically modified (ORMOSIL) sol gel silica exhibited promising properties as negative contrast agents (CA) for MRI applications.The potentiality of these new core–shell NPs as negative CA for MRI is demonstrated and quantified.The longitudinal and transverse relaxivities of NPs with three different coating compositions were studied at a 7 T magnetic field: silica (TEOS), (3-aminopropyl) triethoxysilane (APTES) and (3-glycidoxypropyl) methyldiethoxysilane (GPTMS).Clearly, it was found that the core–shell NPs efficiency as CA was strongly depend on the SPIONs coating.All the three core–shell NPs studied presented a very small effect on the longitudinal relaxation time but a pronounced one on the transverse relaxation time, leading to a very high transverse longitudinal relaxivities ratio, decisive for their efficiency as negative CA for MRI.The effect of the core–shell NPs on the MRI contrast enhancement is obtained and quantified in a set of MRI of agar phantoms obtained at 7 T magnetic field and with a imaging gradient field of 1.6 T/m. The core–shell NPs were tested in Zebra-fish (Danio rerio) animal model. Zebra-fish MRI were obtained with animals injected with the three core–shell NPs and the contrast enhancement validated.

Synthesis, Characterization, and Application of Core-Shell Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents.

Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM–1 s–1 at 3T, a high affinity to [18F]-fluoride or radiometal-bisphosphonate conjugates (e.g., 64Cu and 99mTc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co0.16Fe2.84O4@NaYF4(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe3O4@NaYF4(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

Graphene oxide-Fe3O4 nanoparticle composite with high transverse proton relaxivity value for magnetic resonance imaging

The potential of graphene oxide–Fe3O4 nanoparticle (GO-Fe3O4) composite as an image contrast enhancing material in magnetic resonance imaging has been investigated. Proton relaxivity values were obtained in three different homogeneous dispersions of GO-Fe3O4 composites synthesized by precipitating Fe3O4 nanoparticles in three different reaction mixtures containing 0.01 g, 0.1 g, and 0.2 g of graphene oxide. A noticeable difference in proton relaxivity values was observed between the three cases. A comprehensive structural and magnetic characterization revealed discrete differences in the extent of reduction of the graphene oxide and spacing between the graphene oxide sheets in the three composites. The GO-Fe3O4 composite framework that contained graphene oxide with least extent of reduction of the carboxyl groups and largest spacing between the graphene oxide sheets provided the optimum structure for yielding a very high transverse proton relaxivity value. It was found that the GO-Fe3O4 composites possessed good biocompatibility with normal cell lines, whereas they exhibited considerable toxicity towards breast cancer cells.

High Specific Absorption Rate and Transverse Relaxivity Effects in Manganese Ferrite Nanoparticles Obtained by an Electrochemical Route

Superparamagnetic iron oxide-based nanoparticles (SPIONS) have attracted an enormous amount of attention for their potential use in biomedical applications, due to their good biocompatibility and low toxicity. The current study considers citric acid-conjugated manganese ferrite and its synergy to be used in MRI and in hyperthermia treatment, thus showing theragnostic applications. High colloidal stability was obtained with this functionalization. SPIONS with superparamagnetic behavior of crystal sizes of approximately 20 nm were obtained via an electrochemical synthesis method. One of the highest specific absorption rate (SAR) values was achieved in this work (1661 W g–1), under a magnetic field of 30 mT at 717 kHz frequency, compared with other magnetic ferrites in the literature. These nanoparticles dissipate heat through Néel relaxation and, together with the high SAR value obtained, indicate an excellent material for hyperthermia treatment of cancer. In addition, these nanoparticles exhibit transverse relaxivity behavior, with an r2 value of 394 mM–1 s–1, i.e., at least two times higher than the value of a commercial magnetic contrast agent based on iron oxides. Finally, no toxicity effects of these nanoparticles are evidenced; as a result, these nanoparticles are appropriate for in vivo application.

Prototropic Exchange Governs T1 and T2 Relaxivities of a Potential MRI Contrast Agent Nanozeolite Gd−LTL with a High pH Responsiveness

Aqueous suspensions of lanthanide exchanged zeolite LTL have been investigated by 1H, 17O NMR, and EPR relaxivity studies. Both the longitudinal and the transverse relaxivity of these Gd3+ loaded materials are strongly pH dependent and therefore, they have great potential as pH responsive contrast agents. For example, LTL-nanocrystals loaded with 3.5 wt % Gd show a dramatic decrease in the longitudinal relaxivity from 32 to 7 s–1 mM–1 (7.5 T and 25 °C) when going from pH 4 to 9. 1H and 17O NMR show that this phenomenon can be rationalized by a decrease in proton mobility between the zeolite interior and the exterior due to a change from a fast prototropic exchange to a 3 orders of magnitude slower water exchange mechanism. The same material also has a high transverse relaxivity (98 s–1 mM–1 at 7.5 T, 25 °C, and pH 5 as measured with the CPMG pulse sequence), which is governed by proton exchange too, while water diffusion plays a minor role. The high relaxivities and pH dependence render Gd-loaded LTL mate...

TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis

The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA–NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100‐fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10‐fold) by mild, localized heating resulting from the exposure of tPA–NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA–NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10–3 m−1 s−1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA–NCs a promising nano‐theranosis agent in thrombotic disease.