To overcome the BBB and the limitation of the current clinical image modalities (ie, MRI, PET, CT) that can only resolve a tumor size of ≥2 mm1,2, the novel nanoparticles IL-13-liposomes-magnevist-doxorubicin (IL-13-lip-magnevist-dox) were generated that could be as both a MRI contrast and a chemotherapeutic agent for specifically detection and treatment of early glioma. Based on previous works: 1) interleukin-13 receptor alpha 2 (IL-13Rα2) was over-expressed in glioma cells with 30,000 binding sites each cell3, 2) IL-13-liposomes-doxorubicin inhibited an intracranial glioma growth in mice model4, 3) IL-13-liposomes-Magnevist detected glioma in its early stage in T1 weighted MRI5, we conjugated of IL-13 with liposomes and encapsulated the magnevist and doxorubicin that allow us to target, concomitantly detect and monitor the drug in action.Preparation of IL-13-lip-magnevist-dox referred4,5. The morphology and size were studied by Transmission Electronic microscopy. The concentration of Gd was quantified using ICPAES. The concentration of dox was measured by Soft Max Pro SpectraMaxGEMNI (470-582nm). The signal noise ratio was calculated by study the relaxivity through 7T MRI system (Bruker Biospin 7/20a, Ettlingen, Germany). The relaxivity results from the Magnevist and IL-13-liposomes-magnevist-doxorubicin were compared as the samples were diluted according to the concentration required and exposed to the MRI. The data was acquired on a 7T MRI system . The uptake of IL-13-lip-magnevist-dox was performed. U251 (4000cells/well) and T3691 (150,000cells/well) were attached in four well chamber slides overnight. Then IL-13-lip-magnevist-dox (lipids 0.4mg/mL media) was exposed to the cells for 1h. The cells were fixed and exposed to confocal to obtain the images. Cytotoxicity of IL-13-lip-magnevist-dox in U251, U87 and T3691 were studied by Alamar blue assay (wave length excitation 560nm - emission 590nm). Day1, the cells (12,000cell/well) in 96 well plates were attached overnight. Day2, the particles were exposed to the cells, Alamar blue assay was performed 24, 48 and 72 hours post the exposure of the drugs.IL-13-lip-magnevist-dox are spherical in shape and 100-130 nm in size as shown in Fig.1. The Gadolinium concentration in the liposome was in the range of 4.0-10.0 mg/L for different batches. The concentration of doxorubicin inside the liposomes is 0.2-0.5mg/mL. The MRI relaxivity of IL-13-lip-magnevist-dox from MRI is 4.0 L/mM/s comparing to 4.8 L/mM/s for Magnevist. IL-13-lip-magnevist-dox was internalized by the glioma cell. Fig.2a-d images indicated the nuclei of glioma cells in blue color exposed to DAPI as the control. Fig. 2e-h images shown that the FITC labelled liposomes delivered Rhodamine labelled doxorubicin into the glioma cells. Fig. 2i-t images presented the same results with a glioma stem cell T3691. Fig. 2q-t images shown that the same stem cells were exposed to free Rhodamine labelled doxorubicin as positive control. IL-13-liposomes-megnevist-doxorubicin inhibited the glioma cell growth as shown in Fig. 3. For the mouse tumor model study, Fig. 4 shows clear differences between time-course of MRI contrast change post injection of Magnevist (black line) and those of two consecutive injections of our liposome 24 hrs apart. The image contrast in the tumor remained high at 24 hrs post-injection of IL-13-lip-magnevist-dox (first time point in the red line). Second injection of our liposome further enhanced the tumor contrast. Magnevist is known to be extracellular in tissue and signal enhancement peaked at about 30 mins post-injection. For our liposomes, it appears consisting of two components: one is extracellular with its temporal behavior similar to that of Magnevist; one is intracellular with more sustained enhancement period. The comparison of free Magnevist and IL-13-lip-magnevist-dox, our novel targeted IL-13-lip-magnevist-dox is capable of generating the same level of contrast as free Magnevist. IL-13-lip-magnevist-dox was internalized by the glioma cell as demonstrated in Fig. 2, which indicated IL-13-lip carried the doxorubicin into cells. Figure 3 validated the results by showing IL-13-lip-magnevist-dox as chemotoxin effectively inhibited the tumor cells (U251 and U87 and T3691) proliferation. As indicated in the time-course of in vivo study in Fig. 4, IL-13-lip-magnevist-dox, at least part of it, became internalized in the tumor cells, which would allow directly visualizing the drug distribution and its therapeutic function in the tumor model. IL-13-lip-magnevist-dox, as an effective theranostic tool that is able to specifically target, concomitantly detect and treat infiltrating glioma in its early stage when BBB is still intact. tyle='mso-bidi-font-weight:normal'> IL-13-lip-magnevist-dox as chemotoxin effectively inhibited the tumor cells (U251 and U87 and T3691) proliferation. As indicated in the time-course of in vivo study in Fig. 4, IL-13-lip-magnevist-dox, at least part of it, became internalized in the tumor cells, which would allow directly visualizing the drug distribution and its therapeutic function in the tumor model.