Nanosized Contrast Agents Research Articles

Self-Folding Macromolecular Drug Carrier for Cancer Imaging and Therapy.

Nano-sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano-carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self-folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self-folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti-tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self-folding molecular design underscore its promise for cancer diagnosis and treatment.

Facilitated encapsulation of a nonionic contrast agent for X-ray computed tomography into lipid vesicles by the multiple emulsification-solvent evaporation method

We studied the encapsulation of iohexol (Ihex), a nonionic contrast agent used for X-ray computational tomography, into lipid vesicles using the multiple emulsification-solvent evaporation method to formulate a nanosized contrast agent. This lipid vesicle preparation method consists of three steps: (1) primary emulsification for producing water-in-oil (W/O) emulsions containing fine water droplets that will be converted to the internal water phase of the lipid vesicles, (2) secondary emulsification for formulating multiple water-in-oil-in-water (W/O/W) emulsions encapsulating the fine water droplets containing Ihex, and (3) solvent evaporation to remove the oil phase solvent (n-hexane) and to form lipid bilayers surrounding the fine inner droplets, resulting in the formation of lipid vesicles encapsulating Ihex. As the diameter and Ihex concentration of the primary W/O emulsion droplets decreased, a higher Ihex encapsulation yield was obtained for the final lipid vesicles. The entrapment yield of Ihex in the final lipid vesicles varied significantly with the emulsifier (Pluronic® F-68) concentration in the external water phase of W/O/W emulsion, and the highest yield (65%) was obtained when the emulsifier concentration was 0.1 wt%. We also investigated the powderization of lipid vesicles encapsulating Ihex via lyophilization. The powderized vesicles were dispersed in water after rehydration and maintained their controlled diameters. The entrapment yield of Ihex in powderized lipid vesicles was maintained for over 1 month at 25 ˚C, while significant leakage of Ihex was observed in the lipid vesicles suspended in the aqueous phase.

Plasmonically enhanced two-photon absorption induced photoacoustic microscopy with laser-synthesized TiN nanoparticles

Combining photonic excitation and acoustic detection, photoacoustic imaging (PAI) presents one of the most promising noninvasive biomedical diagnostic modalities, but this technique still lacks efficient nano-sized contrast agents absorbing light in the region of relative tissue transparency (630–900 nm). Here, we explore the use of titanium nitride (TiN) nanoparticles (NPs) fabricated by methods of pulsed laser ablation in liquids as a contrast agent in PAI. When prepared in acetone, the NPs are spherical, have an average size of 25 nm, and exhibit a broad plasmonic absorption peak around 700 nm. We show that solutions of these NPs render possible a strong nonlinear photoacoustic response and the generation of photoacoustic images with 67 μm resolution within the biological transparency window. The observed effect is explained by a plasmonically enhanced two-photon absorption process in TiN NPs. Combined with earlier demonstrated capability of generating photothermal therapeutic effect, relative chemical purity, and excellent biocompatibility, laser-synthesized TiN NPs promise attractive applications in biomedical theranostics involving imaging modalities based on photoacoustics microscopy or tomography.

Insight into Sonoluminescence Augmented by ZnO-Functionalized Nanoparticles.

Recent advances in optical imaging techniques rely on the use of nanosized contrast agents for in vitro and in vivo applications. We report on an imaging method based on the inertial cavitation of ultrasound-irradiated water solutions that lead to sonoluminescence (SL), here, newly proposed in combination with semiconductor nanoparticles, in particular, aminopropyl-functionalized zinc oxide nanocrystals. The obtained measurements confirm the ability of such nanocrystals to increase the sonoluminescence emission, together with the ability to modify the SL spectrum when compared to the pure water behavior. In particular, it is shown that the UV component of SL is absorbed by the semiconductor behavior that is also confirmed in different biologically relevant media. Finally, optical images of nanocrystal-assisted SL are acquired for the first time, in particular, in biological buffers, revealing that at low ultrasound intensities, SL is measurable only when the nanocrystals are present in solution. All of these results witness the role of amine-functionalized zinc oxide nanocrystals for sonoluminescence emission, which makes them very good candidates as efficient nanocontrast agents for SL imaging for biological and biomedical applications.

Nanosized Contrast Agents in Ultrasound Molecular Imaging.

Applying nanosized ultrasound contrast agents (nUCAs) in molecular imaging has received considerable attention. nUCAs have been instrumental in ultrasound molecular imaging to enhance sensitivity, identification, and quantification. nUCAs can achieve high performance in molecular imaging, which was influenced by synthetic formulations and size. This review presents an overview of nUCAs from different synthetic formulations with a discussion on imaging and detection technology. Then we also review the progress of nUCAs in preclinical application and highlight the recent challenges of nUCAs.

Construction of novel amphiphilic chitosan-polylactide graft copolymer nanodroplets for contrast enhanced ultrasound tumor imaging.

In this experiment, a new amphiphilic chitosan-poly(lactide) graft copolymer was synthesized and characterized by IR, 1H-NMR, XRD, TGA. The obtained chitosan-poly (lactide) graft copolymer was used as the matrix material to prepare nanodroplets (NDs) encapsulating with liquid PFP by double-emulsion and solvent evaporation method. The resulting NDs were characterized by photon correlation spectroscopy and transmission electron microscopy (TEM). The biocompatibility was explored by cytotoxicity assay, cell migration assay and blood biochemistry analysis. The experiments of ultrasonic imaging in vitro and in vivo were carried out with a B-mode clinical ultrasound imaging system. The results of FI-IR and 1H-NMR confirmed the successful grafting reaction of polylactic acid(PLLA) to chitosan with a graft rate of 365%. The average size of the NDs was 101.1 ± 2.7 nm, with the polydispersity index (PDI) of 0.127 ± 0.020, and the zeta potential was -31.8 ± 1.5 mV. From the TEM results, NDs were highly dispersed and had a spherical shape with a distinct capsule structure. The NDs exhibited good stability during storage at 4°C. The NDs solution with different concentrations did not affect cell growth and showed good biocompatibility in cytotoxicity, cell migration and blood biochemistry studies. Under the irradiation of ultrasonic waves, the NDs formed an ultrasonic high signal, which could significantly enhance the ultrasound imaging of tumor tissue in vivo. Taken together, the NDs hold great potential for ultrasound imaging as a nanosized contrast agent.

Preparation and Evaluation of New LAT1-Targeted USPION to Improve Sensitivity and Specificity in Metabolic Magnetic Imaging of Breast Cancer

The purpose of this study was the investigation of the targeting potential of tyrosine-conjugated ultra small superparamagnetic iron oxide nanoparticles (USPIONs) as a new targeted nano-contrast agent for application in molecular magnetic resonance imaging (MRI) of breast cancer. Recently, studies demonstrated that L-type amino acid transporters (LAT1) are highly expressed in breast cancer cells. Thus, LAT1 targeting via tyrosine as a LAT1 substrate could improve the sensitivity and specificity of this nanosized contrast agent. To achieve this goal, USPIONs were conjugated to tyrosine and characterized using DLS and FT-IR. The cell viability was measured in different concentrations of nanoparticles (0.6, 1.2, 2.4mM) in breast cancer cells (MDA231, MCF7,4T1) and control cell line (normal kidney cells; HEK293) with the MTT assay. Cellular uptake was evaluated via Prussian blue staining and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) as well as by measurement of the reduction of signal intensity using 3Tesla clinical MRI. T2-weighted imaging in tumor-bearing bulb/c mice was performed via brain coil and home-built phantom. The particle size and charge of USPIO significantly changed after the conjugation of tyrosine. According to ICP-OES results from the cellular uptake of tyrosine-USPION in 4T1 cell line and HEK-293was 48.14%±1.43, and 6.91±0.21, respectively. The reduction in MRI signal intensity at in vitro studies was higher in the presence of tyrosine-USPION than of USPION. The reduction in MRI signal intensity at in vivo studies was 58.83% in the presence of tyrosine conjugated USPION compared with plain nanoparticles. Biodistribution studies demonstrated that the accumulation of tyrosine-USPIONs was about seven times higher than that of non-targeted USPIONs after 24h. In conclusion, tyrosine-USPIO as a new LAT1 targeted contrast agent with high sensitivity and specificity can be suggested as a good and ideal candidate in breast cancer molecular imaging.

Recent Advances of Bioresponsive Nano-Sized Contrast Agents for Ultra-High-Field Magnetic Resonance Imaging.

The ultra-high-field magnetic resonance imaging (MRI) nowadays has been receiving enormous attention in both biomaterial research and clinical diagnosis. MRI contrast agents are generally comprising of T1-weighted and T2-weighted contrast agent types, where T1-weighted contrast agents show positive contrast enhancement with brighter images by decreasing the proton's longitudinal relaxation times and T2-weighted contrast agents show negative contrast enhancement with darker images by decreasing the proton's transverse relaxation times. To meet the incredible demand of MRI, ultra-high-field T2 MRI is gradually attracting the attention of research and medical needs owing to its high resolution and high accuracy for detection. It is anticipated that high field MRI contrast agents can achieve high performance in MRI imaging, where parameters of chemical composition, molecular structure and size of varied contrast agents show contrasted influence in each specific diagnostic test. This review firstly presents the recent advances of nanoparticle contrast agents for MRI. Moreover, multimodal molecular imaging with MRI for better monitoring is discussed during biological process. To fasten the process of developing better contrast agents, deep learning of artificial intelligent (AI) can be well-integrated into optimizing the crucial parameters of nanoparticle contrast agents and achieving high resolution MRI prior to the clinical applications. Finally, prospects and challenges are summarized.

Surface-modified GVs as nanosized contrast agents for molecular ultrasound imaging of tumor

Nanobubbles, as a kind of new ultrasound contrast agent (UCAs), have shown promise to penetrate tumor vasculature to allow for targeted imaging. However, their inherent physical instability is an ongoing concern that could weaken their imaging ability with ultrasound. Gas vesicles (GVs), which are genetically encoded, naturally stable nanostructures, have been developed as the first ultrasonic biomolecular reporters which showed strong contrast enhancement. However, further development of tumor imaging with GVs is limited by the quick clearance of GVs by the reticuloendothelial system (RES). Here, we developed PEGylated HA-GVs (PH-GVs) for in-tumor molecular ultrasound imaging by integrating polyethylene glycol (PEG) and hyaluronic acid (HA) in GV shells. PH-GVs were observed to accumulate around CD44-positive cells (SCC7) but not be internalized by macrophage cell line RAW 264.7. Green fluorescence from PH-GVs was found around cell nuclei in the tumor site after 6 h and the signal was sustained over 48 h following tail injection, demonstrating PH-GVs’ ability to escape the clearance from the RES and to penetrate tumor vasculature through enhanced permeability and retention (EPR) effects. Further, PH-GVs produced strong ultrasound contrast in the tumor site in vivo, with no obvious side-effects detected following intravenous injection. Thus, we demonstrate the potential of PH-GVs as novel, nanosized and targeted UCAs for efficient and specific molecular tumor imaging, paving the way for the application of GVs in precise and personalized medicine.

Manganese-doped cesium iodide nanoparticles for multi-model bioimaging

Abstract The severe threat posed by heavy-metal-containing alkali halides to environment and humans demands heavy-metal-free alkali halides without compromising their exceptional optoelectronic characteristics. In this study, manganese doped cesium iodide (CsI:Mn2+) nanoparticles (NPs) were synthesized via the hot injection method, while retaining their optoelectronic attributes. Results corroborate manganese doping has no noticeable effect on blue emission of CsI NPs and shows well-dispersed particles with an average size of 10 nm. Due to the strong fluorescence, the CsI:Mn2+ NPs can be used for cell imaging, and have demonstrated the exceptional computed X-ray tomography (CT) and magnetic resonance imaging (MRI) imaging potential as compared to the conventional clinical and nanosized manganese contrast agents. These findings have thus broadened the scope of potential biomedical applications of this kind of NPs for theranostics.

In Vivo Examination of Folic Acid-Conjugated Gold-Silica Nanohybrids as Contrast Agents for Localized Tumor Diagnosis and Biodistribution.

Enhanced biocompatibility of nanosized contrast agent with high radiodensity and specific biodistribution is an important parameter for localized tumor imaging and organ safety. Various nanoparticles, especially gold nanorods (GNRs), have been applied for tumor diagnosis. However, their toxicity, nonspecific biodistribution, and easy aggregation are critical issues in cancer medicine. To avoid these issues, encapsulation of the GNRs in the core of nanoscopic mesoporous silica (MS) under ambient conditions, yielding multifunctional nanomaterials for cancer nanomedicine, is a recent and active development. Interestingly, GNR embedded MS nanohybrid (GNR-MS), though a promising material in nanomedicine, is rarely examined for tumor diagnosis, in vivo toxicity, organ safety, contrast ability, and excretion. Herein, we report a systematic in vivo examination of folic acid functionalized GNR-MS (GNR-MS-FA) for localized 4T1 breast tumor diagnosis, organ safety, and excretion using a one-time dose administration. The nanomaterials show good aqueous dispersibility, biocompatibility, high radiodensity, and tumor specific targeting ability ( in vitro as well as in vivo). The in vivo tumor diagnosis and specific biodistribution of injected nanomaterials clearly demonstrates their potential for the visualization of tumors deep in the body of mice. In addition, all organs including the healthy glomerulus of the kidney are observed to be free of tissue injuries thereby indicating the superior biocompatibility of the nanomaterials.

Highly stable and biocompatible nanocontrast agent encapsulating a novel organic fluorescent dye for enhanced cellular imaging

Conventional organic dyes and inorganic fluorescent contrast agents have been hampered in bioimaging and biomedical purposes due to their intrinsic drawbacks. Thus there is a pressing need to develop novel classes of fluorescent contrasts with merits of high photostability and good biocompatibility for biomedical applications. In this study, we report the fabrication of a nanosized contrast agent (Tnano) loaded with a novel organic fluorescent dye (TPACN) and evaluation of its performance for cellular imaging. This nanocontrast agent not only preserved the optical characters of TPACN, including superior fluorescence quantum yield (QY) of 67% and large Stokes shift of 165 nm, but also exhibited remarkable colloidal and fluorescence stabilities compared to free TPACN, and superior biocompatibility and enhanced cellular imaging capacity as well. Given these favorable properties, our TPACN-loaded nanocontrast agent might potentially be applied for bioimaging and biomedical use in the future.

Contrast-enhanced magnetic resonance imaging with a novel nano-size contrast agent for the clinical diagnosis of patients with lung cancer.

Recent studies have indicated that magnetic resonance imaging (MRI) efficiently diagnoses lung cancer. However, the efficacy of MRI in diagnosing lung cancer requires improving for patients in the early stage of the disease. In the present study, a novel nano-sized contrast agent of chistosan/Fe3O4-enclosed bispecific antibodies (BsAbCENS) was introduced, which targeted carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) in lung cancer cells. The diagnostic efficacy of contrast-enhanced MRI with BsAbCENS (CEMRI-BsAbCENS) was investigated in a total of 182 patients with suspected lung cancer who had high serum levels of CEA and NSE. BsAbCENS was administered by pulmonary inhalation prior to the MRI scan. The results revealed that CEA and NSE were overexpressed in human lung cancer cell lines. BsAbCENS bound with CEA and NSE on the surface of human lung cancer cells and produced a higher signal intensity than MRI alone for the diagnosis of patients with lung cancer. The diagnostic data revealed that CEMRI-BsAbCENS diagnosed 124/182 lung cancer cases, whereas CEMRI only diagnosed 98/182, which was significantly less (P<0.01). In addition, the survival rate of patients with lung cancer diagnosed by CEMRI-BsAbCENS was significantly higher than the mean 5-year survival rate (P<0.01). Furthermore, the pharmacodynamics demonstrated that BsAbCENS was metabolized within 24 h. The results of the present study indicate that the efficacy and accuracy of lung cancer diagnosis are improved by CEMRI-BsAbCENS. In conclusion, these results provide a potential novel protocol for the diagnosis of tumors in patients with suspected early stage lung cancer.

Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer

Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C3F8)-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro, single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo, US imaging signal in the murine breast cancer model was significantly higher (P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo. This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.

Novel Gd-Loaded Silicon Nanohybrid: A Potential Epidermal Growth Factor Receptor Expressing Cancer Cell Targeting Magnetic Resonance Imaging Contrast Agent.

Continuing our research efforts in developing mesoporous silicon nanoparticle-based biomaterials for cancer therapy, we employed here porous silicon nanoparticles as a nanocarrier to deliver contrast agents to diseased cells. Nanoconfinement of small molecule Gd-chelates (L1-Gd) enhanced the T1 contrast dramatically compared to distinct Gd-chelate (L1-Gd) by virtue of its slow tumbling rate, increased number of bound water molecules, and their occupancy time. The newly synthesized Gd-chelate (L1-Gd) was covalently grafted on silicon nanostructures and conjugated to an antibody specific for epidermal growth factor receptor (EGFR) via a hydrazone linkage. The salient feature of this nanosized contrast agent is the capability of EGFR targeted delivery to cancer cells. Mesoporous silicon nanoparticles were chosen as the nanocarrier because of their high porosity, high surface area, and excellent biodegradability. This type of nanosized contrast agent also performs well in high magnetic fields.

Simulated Measurements of the Magnetic Behavior of New Dual-Mode Nanosized Contrast Agents

Aim of this work was to perform simulated measurements of the magnetic behavior of a novel class of bimodal nanosized contrast agents (CAs), made of a silica core covered by smaller superparamagnetic nanoparticles (NPs) and designed to be detected through both ultrasound and magnetic resonance imaging (MRI), in order to compare their performance in terms of MRI signal enhancement with that of the superparamagnetic NPs alone. The considered bimodal nanocomposites consisted of 330-nm silica nanospheres covered by either superparamagnetic iron oxide NPs or dumbbell-like FePt-IO nanocrystals. We simulated the MRI signal generated by each of the considered CAs during a brain venography in standard clinical conditions. Quantitative assessments of signal enhancement were carried out as a function of the main model parameters. The performed numerical simulations showed that the magnetic response of the novel nanocomposites was similar or better compared to that of the superparamagnetic NPs alone for echo times longer than 20 ms, leading to an easier detection of smaller vessels. Obtained results suggest that the bimodal NPs have an exciting potential for the development of innovative clinical protocols for multimodal imaging, combining quantitative measurements of cerebral blood flow and targeted molecular imaging of specific diseases.

Oxygen Vacancy Enables Markedly Enhanced Magnetic Resonance Imaging-Guided Photothermal Therapy of a Gd3+-Doped Contrast Agent.

Gd3+-based contrast agents (CAs) are the most prevailing and widely used for enhanced magnetic resonance imaging (MRI). Numbers of approaches have been developed to regulate the key parameters in order to obtain high-relaxivity CAs, according to the classic Solomon-Bloembergen-Morgen theory. Herein, a method of controlling oxygen vacancies in inorganic nanosized CAs has been developed for largely accelerated proton relaxation to obtain a high r1 value. Such a strategy is verified on oxygen-deficient PEG-NaxGdWO3 nanorods, which exhibit a remarkable r1 value up to 80 mM-1 s-1 (at 0.7 T) and a high r1 value of 32.1 mM-1 s-1 on a clinical 3.0 T scanner, offering an excellent blood pool MRI performance at a low dose. Meanwhile, free electrons and/or oxygen-vacancy-induced small polarons can endow PEG-NaxGdWO3 nanorods with significant photothermal conversion for MRI-guided photothermal therapy.

Recent progress of rare earth-based multi-modal nano-sized contrast agents

Due to the specific electron structure, distinctive optical/electronic/magnetic properties, and related high atomic number, worldwide scientists in various relevant fields have focused on the rational design of rare earth-based nano-sized contrast agents and their biomedical imaging application recently. For a long time, rare earth-doped nanoprobes have been widely used in up-conversion luminescence imaging owing to their attractive 4f electrons. Gd3+-modified nanoprobes and Gd3+-based nanomaterials with the unpaired 4f electrons have been generally used as contrast agents for T1-weighted MR imaging. In addition, rare earth-based nanosturcturs have performed well in X-ray imaging and CT imaging due to their stronger X-ray attenuation and higher atomic number than those of routinely used small iodinated molecules. This review provides a comprehensive introduction to the recent development of novel rare earth-based multi-modal nano-sized contrast agents, and their usages in the field of biomedical imaging.

In vivo tumor targeting and biodistribution evaluation of paramagnetic solid lipid nanoparticles for magnetic resonance imaging

The current study was performed to evaluate the in vivo efficiency of a new nano-sized contrast agent called paramagnetic Solid Lipid Nanoparticles, pSLNs, having promising relaxivity properties for Magnetic Resonance Imaging application. Good stability and stealth properties toward macrophage uptake have been demonstrated. An in vivo MRI study resulted in an improved signal enhancement in the tumor tissue particularly when folate as targeting ligand was used to decorate the nanoparticles surface. Afterward, the biodistribution of pSLNs in several organs was investigated. The accumulation of pSLNs in kidneys, femoral bones, spleen and brain was quite low while high tropism of pSLNs was found for the liver. In this regard, approaches to improve the rate of the hepatic clearance have been proposed.

Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats.

The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T2 relaxation rate (r2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM−1 s−1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly showed the retention of Lf-M-PAEEP-PLLA-NPs in tumor tissues. The results from the in vitro and in vivo MRI indicated that Lf-M-PAEEP-PLLA-NPs possessed strong, long-lasting, tumor targeting, and enhanced tumor MRI contrast ability. Lf-M-PAEEP-PLLA-NPs represent a promising nano-sized MRI contrast agent for brain glioma targeting MRI.