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Confocal microscopy of (a) bright-field, fluorescent with excitation wavelengths of (b) 488 and (c) 543 nm, and (d) merged images for A549 cells after incubation with 50 μg/mL FeMn(SiO 4 ) hollow nanospheres for 24 h. (e−h) Subcellular localization of FeMn(SiO 4 ) hollow nanospheres observed by a confocal fluorescent microscopy. A549 cells transfected with mcherry-LAMP-1 were incubated with FeMn(SiO 4 ) hollow nanospheres for 24 h. (f) Fluorescence image of FeMn(SiO 4 ) hollow nanospheres. (g) Fluorescence image of mcherry-LAMP-1. (h) The overlap of the mcherry-LAMP-1 and FeMn(SiO 4 ) hollow nanospheres images indicates the colocalization of lysosomes and FeMn(SiO 4 ) hollow nanospheres. (In this experiment, we find that the luminous intensity of the nanospheres is weaker than that of mcherry-LAMP-1 with same intensity of excitation light. With the parameter of laser output set as 10%, the red fluorescence of mcherry-LAMP-1 can be observed obviously, while the red fluorescence of nanospheres is weak and almost invisible. Then, the parameter of laser output for FeMn(SiO 4 ) hollow nanospheres imaging was set as 15%. The parameter of laser output for mcherry-LAMP-1 imaging was set as 10%. Thus, the interference to the fluorescence image of mcherry-LAMP-1 induced by FeMn(SiO 4 ) hollow nanospheres could be eliminated through setting imaging parameters as mentioned above.). 

Confocal microscopy of (a) bright-field, fluorescent with excitation wavelengths of (b) 488 and (c) 543 nm, and (d) merged images for A549 cells after incubation with 50 μg/mL FeMn(SiO 4 ) hollow nanospheres for 24 h. (e−h) Subcellular localization of FeMn(SiO 4 ) hollow nanospheres observed by a confocal fluorescent microscopy. A549 cells transfected with mcherry-LAMP-1 were incubated with FeMn(SiO 4 ) hollow nanospheres for 24 h. (f) Fluorescence image of FeMn(SiO 4 ) hollow nanospheres. (g) Fluorescence image of mcherry-LAMP-1. (h) The overlap of the mcherry-LAMP-1 and FeMn(SiO 4 ) hollow nanospheres images indicates the colocalization of lysosomes and FeMn(SiO 4 ) hollow nanospheres. (In this experiment, we find that the luminous intensity of the nanospheres is weaker than that of mcherry-LAMP-1 with same intensity of excitation light. With the parameter of laser output set as 10%, the red fluorescence of mcherry-LAMP-1 can be observed obviously, while the red fluorescence of nanospheres is weak and almost invisible. Then, the parameter of laser output for FeMn(SiO 4 ) hollow nanospheres imaging was set as 15%. The parameter of laser output for mcherry-LAMP-1 imaging was set as 10%. Thus, the interference to the fluorescence image of mcherry-LAMP-1 induced by FeMn(SiO 4 ) hollow nanospheres could be eliminated through setting imaging parameters as mentioned above.). 

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Magnetic resonance (MR) imaging probes can be concentrated in tumors through grafting targeting agents. However, the clinical application of such targeted MRI probes is largely limited because specific agents are only used to target specific characteristics of cancer cells. The development of the MR imaging probes which can be used regardless of tu...

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... human lung cancer cells treated with FeMn(SiO 4 ) hollow nanospheres were imaged under a confocal laser scanning microscopy (CLSM) to further study the in vitro bioimaging properties of the nanospheres. Green and red fluorescence (Figure 9b,c) are observed under the laser excitation with different wavelengths (488 and 543 nm). Combined with the luminescent results mentioned above, the generation of bright red fluorescence indicates that FeMn- (SiO 4 ) hollow spheres are taken up by A549 cells and Mn 2+ ions are released in the acidic organelles. ...
Context 2
... with the luminescent results mentioned above, the generation of bright red fluorescence indicates that FeMn- (SiO 4 ) hollow spheres are taken up by A549 cells and Mn 2+ ions are released in the acidic organelles. The overlay of the bright field and fluorescent images (Figure 9d) verifies that the luminescence is originated from the intracellular region. ...

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... At the end of the experiment, major organs, including liver, lung and kidney, were isolated from all treatments along with the cancer control group that received no treatment and also from normal mice. After the preparation of tissue histology slides, HE staining was performed to compare the effect of different treatment groups by analyzing pathological changes in tissue morphology [29]. All animal studies were executed under a protocol approved by the DFCI Institutional Animal Care and Use Committee (IACUC) guidelines. ...
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Bortezomib (BTZ) is a standard-of-care treatment in multiple myeloma (MM); however, adverse side effects and development of resistance limit its long term benefit. To improve target specificity, therapeutic efficacy, and overcome resistance, we designed nanoparticles that encapsulate BTZ and are surface-functionalized with BCMA antibodies (BCMA-BTZ-NPs). We confirmed efficient cellular internalization of the BCMA-BTZ-NPs only in BCMA-expressing MM cells, but not in BCMA-knockout (KO) cells. In addition, BCMA-BTZ-NPs showed target-specific cytotoxicity against MM cell lines and primary tumor cells from MM patients. The BCMA-BTZ-NPs entered the cell through receptor-mediated uptake, which escapes a mechanism of BTZ resistance based on upregulating P-glycoprotein. Furthermore, BCMA-BTZ-NPs induced cell death more efficiently than non-targeted nanoparticles or free BTZ, triggering potent mitochondrial depolarization followed by apoptosis. In BTZ-resistant cells, BCMA-BTZ-NPs inhibited proteasome activity more effectively than free BTZ or non-targeted nanoparticles. Additionally, BCMA-BTZ-NPs enhanced immunogenic cell death and activated the autophagic pathway more than free BTZ. Finally, we found that BCMA-BTZ-NPs selectively accumulated at the tumor site in a murine xenograft model, enhanced tumor reduction, and prolonged host survival. These results suggest BCMA-BTZ-NPs provide a promising therapeutic strategy for enhancing the efficacy of BTZ and establish a framework for their evaluation in a clinical setting.
... At the end of the experiment, major organs, including liver, lung and kidney, were isolated from all treatments along with the cancer control group that received no treatment and also from normal mice. After the preparation of tissue histology slides, HE staining was performed to compare the effect of different treatment groups by analyzing pathological changes in tissue morphology [29]. All animal studies were executed under a protocol approved by the DFCI Institutional Animal Care and Use Committee (IACUC) guidelines. ...
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Bortezomib (BTZ) is a standard-of-care treatment for multiple myeloma (MM). In addition to its direct anti-MM effects, we recently reported that BTZ triggers immunogenic cell death associated with improved outcome. However, adverse effects limit its long-term clinical use. To improve its therapeutic index, we encapsulated bortezomib in PEG-PLGA nanoparticles linked with antibodies that target B-cell maturation antigen (BCMA-BTZ-NPs) to specifically target MM cells. BCMA-BTZ-NPs showed significantly increased cellular internalization into wild-type (WT) H929 cells after 6h (99.2±0.7%) than non-targeted NPs (57.7±0.8%) (p<0.0001), with a time-dependent increase in internalization. Importantly, cellular internalization of the BCMA-BTZ-NPs in BCMA-KO H929 cells (15.9±2.5%) was significantly depleted (p<0.0001). BCMA-BTZ-NPs showed target-specific cytotoxicity against MM cell lines and primary tumor cells from MM patients. Furthermore, BCMA-BTZ-NPs induced cell death more efficiently than non-targeted nanoparticles or free BTZ, triggering potent mitochondrial depolarization assessed by JC1 staining in MM.1S (79.06±3.7% vs. 57.4±1.9% for BCMA-BTZ-NPs vs non-targeted NPs, p<0.01); and H929 cells (47.23±1.9% vs. 31.26±0.7% for BCMA-BTZ-NPs vs. non-targeted NPs, p<0.001). This was associated with enhanced activation of caspases 8, 9 and 3, followed by apoptosis. We also found that BCMA-BTZ-NPs were still effective in BTZ-resistant MM cell lines (36.66±1.8% residual chymotryptic activity in RPMI-Dox40 [resistant] and 40.29±1.0% in MM.1S [sensitive] cells), whereas free BTZ showed no inhibitory effect (100.01±4.6% residual chymotryptic activity in RPMI-Dox40), likely due to BCMA-BTZ-NPs entering the cell through receptor-mediated uptake which averts acquired BTZ resistance based on the drug pump P-glycoprotein (PgP). Importantly, BCMA-BTZ-NPs also enhanced immunogenic cell death (ICD) and activated the autophagic pathway more than free BTZ, evidenced by increased calreticulin cell surface exposure (free BTZ: 45.13±3.7% vs BCMA-BTZ-NP: 71.5±3.4%,) and induction of T-cell proliferation in both MM.1S (free BTZ: 36.5±2.6% vs. BCMA-BTZ-NP: 65.2±2.3%, p<0.001) and AMO-1 cells (free BTZ: 37.03±1.3% vs. BCMA-BTZ-NP: 66.33±3.3%, p<0.001). Of note, increased levels of TNFα, Granzyme B, and IFNγ were also present in BCMA-BTZ-NPs treated MM cells with DC (Dendritic cells) and T cells co-culture supernatants. Finally, we evaluated the in vivo target selectivity and therapeutic efficacy of BCMA-BTZ-NPs against human MM cells in a murine xenograft model. BCMA-BTZ-NPs selectively accumulated in the tumor more efficiently than non-targeted BTZ-NPs and were associated with more efficient tumor reduction and host survival. In summary, our study indicates that BCMA-BTZ nanotherapy accumulates at the tumor site, enhances therapeutic efficacy, triggers immunogenic cell death, overcomes drug resistance, and reduces off-target toxicity. These results provide the framework for clinical evaluation of BCMA-BTZ-NPs to increase the therapeutic index of BTZ and improve patient outcome in MM.
... The obtained product has high purity, good dispersibility, and controllable size; however, it has a long reaction cycle and is highly dependent on the production equipment. For example, Chen et al 52 ...
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Manganese (Mn)-based magnetic resonance imaging (MRI) has become a competitive imaging modality for cancer diagnosis due to its advantages of non-invasiveness, high resolution and excellent biocompatibility. In recent years, a variety of Mn contrast agents based on different material systems have been synthesized, and a series of multi-purpose Mn nanocomposites have also emerged, showing satisfactory relaxation efficiency and MRI performance thus possess the transformation and application value in MRI-synergized cancer diagnosis and treatment. This tutorial review starts from the classification and properties of Mn-based nanomaterials, and then summarizes various preparation and functionalization strategies of nanosized Mn contrast agents, especially focuses on the latest progress of Mn contrast agents in MRI-synergized precise cancer theranostics. In addition, present review also discusses the current clinical transformation obstacles such as unclear molecular mechanisms, potential nanotoxicity, and scale production constraints. This paper provides evidence-based recommendations about the future prospects of multifunctional nanoplatforms, as well as technical guidance and panoramic expectations for the design of clinically meaningful cancer management programs.
... In addition, there were no other diffraction peaks in the GdIO sample, indicating that the sample is not a simple physical mixture of Gd2O3 and Fe3O4, and Gd 2+ may occupy the tetrahedral or octahedral position of Fe3O4. Compared to Fe3O4, the diffraction peak of GdIO shifted slightly to the left, which is due to the larger radius of the Gd ion leading to an increase in crystal plane spacing [29], a result that is consistent with earlier outcomes. Fe 3 O 4 and GdIO were synthesized by the same method, and X-ray diffraction (XRD) was used to further analyze the phase structure of the nanoclusters (Figure 2). ...
... In addition, there were no other diffraction peaks in the GdIO sample, indicating that the sample is not a simple physical mixture of Gd 2 O 3 and Fe 3 O 4 , and Gd 2+ may occupy the tetrahedral or octahedral position of Fe 3 O 4 . Compared to Fe 3 O 4 , the diffraction peak of GdIO shifted slightly to the left, which is due to the larger radius of the Gd ion leading to an increase in crystal plane spacing [29], a result that is consistent with earlier outcomes. To achieve tumor targeting and therapeutic effects, a PEG600 diacid modification was made on the surface of the nanoclusters to allow cRGD and DTX binding. ...
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Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1-T2 dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvβ3 on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.
... Since T 1 -and T 2 -weighted contrast agents exhibit great response and possess unique qualities, but there are some reports which have described their limitations. Therefore, synergic integration of these two functions (T 1 and T 2 ) for MRI is expected to get more comprehensive and cooperative diagnostic information over the single T 1 or T 2 contrast agent [19][20][21]. The development of dual-mode contrast agent of MRI in a single instrumental system could proficiently eliminate certain difficulties. ...
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In the biomedical treatment, identification of diseases and their diagnosis are running with help of many biomedical techniques including imaging such as magnetic resonance imaging (MRI). MRI technique requires an identification of targeted cell or lesion area which can be achieved by contrast agent. For clinical use, T1 positive MRI contrast agents and T2 negative MRI contrast agents are being used. However, these contrast agents have several drawbacks such as toxic effect of metal centre, poor resolution, weak contrast, low intensity image and short signal for long-term in vivo measurement. Therefore, development of new contrast agents is imperative. Ionic liquids with their unique properties have been tried as novel contrasting materials. Particularly, iron-containing amino-acid-based ionic liquids or amino-acid-based paramagnetic ionic liquids (PMILs) have been reported and demonstrated as MRI contrast agents. These PMILs have shown superior features over reported contrast agents such as dual-mode contrast, biofriendly nature, involvement of non-toxic magnetic centre (Fe), stable aqueous solution, better image intensity at low concentration level and easy to synthesis. PMILs have been characterized well and studied with animal DNA using various techniques. The result revealed that animal DNA is remain safe and stable structurally up to 5 mmol.l−1. These cost-effective PMILs opened the greater opportunity in the field of contrast-based biomedical applications.
... This enhancement-phase distinction between cancer cells and surrounding tissue help in producing high-contrast enhancement HCC pictures and led to the accurate diagnosis of liver lesions over normal tissues. More studies have also confirmed that Mn 2+ doped MSN can be used as a highly sensitive MRI diagnostic agent (Chen et al., 2012;Chen et al., 2015b;Fei et al., 2020a). In general, SNFs may be effective and less toxic hepatoma-specific MRI contrast agents. ...
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Silica-based nanoframeworks have been extensively studied for diagnosing and treating hepatocellular carcinoma (HCC). Several reviews have summarized the advantages and disadvantages of these nanoframeworks and their use as drug-delivery carriers. Encouragingly, these nanoframeworks, especially those with metal elements or small molecular drugs doping into the skeleton structure or modifying onto the surface of nanoparticles, could be multifunctional components participating in HCC diagnosis and treatment rather than functioning only as drug-delivery carriers. Therefore, in this work, we described the research progress of silica-based nanoframeworks involved in HCC diagnosis (plasma biomarker detection, magnetic resonance imaging, positron emission tomography, photoacoustic imaging, fluorescent imaging, ultrasonography, etc.) and treatment (chemotherapy, ferroptotic therapy, radiotherapy, phototherapy, sonodynamic therapy, immunotherapy, etc.) to clarify their roles in HCC theranostics. Further, the future expectations and challenges associated with silica-based nanoframeworks were highlighted. We believe that this review will provide a comprehensive understanding for researchers to design novel, functional silica-based nanoframeworks that can effectively overcome HCC.
... Recently, manganese silicates have been widely applied in energy storage batteries, supercapacitors, organic catalysis, and drug delivery. [27][28][29][30][31][32] These reports suggest the great potential and tolerance of Mn silicates in diverse chemical environments. Therefore, silicate stabilized Mn sites are assumed to be potential candidates as stable OER catalysts in near-neutral electrolytes. ...
... However, to the best of our knowledge, no such research has yet been reported. Considering the unique nanostructure of manganese silicates and the multivalent state of manganese in the silicates, [28][29][30][31][32][33][34] promising OER catalytic properties can be expected. Therefore, we deem silicate to be a new platform for developing durable Mn-based OER catalysts. ...
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Efficient, stable and cost-effective oxygen evolution catalysts (OECs) operating in near-neutral or weak acid media have highly practical applications in electrochemical (EC) and photoelectrochemical (PEC) fields. However, conventional catalysts are mostly based on precious metals, while those based on earth-abundant elements that are efficient in alkaline solution generally suffer from dissolution in such media. Herein, we show that novel manganese silicate-based film materials prepared from thermal vapor deposition and a subsequent microwave reaction can act as potential oxygen evolution reaction (OER) catalysts in near-neutral media. Pristine manganese silicate displays excellent intrinsic catalytic activity. With W doping, the catalysts exhibit remarkably better apparent catalytic activity as it leads to the exposure of more active sites without impairing the bulk conductivity. W doping also serves to significantly adjust the elementary valence states of Mn and enrich the surface hydroxyl groups, resulting in much improved stability. DFT calculations reveal that the theoretical overpotential of manganese silicate is comparable to that of other reported manganese oxide OER catalysts. These results demonstrate manganese silicates as a new class of OECs for stable water splitting in near-neutral media. They also illustrate a new pathway of improving stability in near-neutral media by introducing high-valency metal elements for the design of nonprecious OEC. This journal is
... For clinical MRI CA, biosafety is a very important factor [30]. The cytotoxicity of GMIO over a wide range of concentrations was investigated using the CCK-8 assay. ...
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Single-mode magnetic resonance imaging (MRI) contrast agents (CAs) in clinical settings are easily disturbed by calcification, bleeding, and adipose signals, which result in inaccurate diagnoses. In this study, we developed a highly efficient T1-T2dual-mode MRI CA using an ultra-small gadolinium oxide-decorated magnetic iron oxide nanocrystal (GMIO). The gadolinium element could effectively alter the magnetic properties of the GMIO from soft-ferromagnetism to superparamagnetism. In addition, when the Gd/Fe ratio was 15 % (designated as GMIO-2), the GMIO-2 possessed the best superparamagnetism and highest magnetism. Subsequently, T1and T2values of GMIO-2 were measured through a series of turbo spin-echo images and then multi-spin echo (MSE) sequence, respectively. Based on this, T1and T2relaxivities of GMIO-2 were calculated and were the highest (r1: 1.306 m M-1s-1and r2: 234.5 m M-1s-1) when compared to other groups. The cytotoxicity of GMIO-2 was negligible under a wide range of dosages, thus exhibiting excellent cell biocompatibility. Moreover, GMIO-2 could quickly diffuse into cells, leading to its effective accumulation. The systemic delivery of GMIO-2 resulted in an excellent T1-T2dual-mode MRI contrast effect in kidneys, which is expected to improve the diagnosis of kidney lesions. Therefore, this work provides a promising candidate for the development of a T1-T2dual-mode MRI CA.
... The group of DiR-PLGA NPs exhibited a gradually fading fluorescent signal in the liver and lungs 8 h after intravenous injection, as compared to the free DiR group. This difference was attributed to the mononuclear phagocyte system (MPS) and EPR effect because of their small size [72,73]. Moreover, because of the membrane coating of cancer cells and macrophages, the fluorescent signals were observed in the lung in the DiR-PLGA@[RAW-4T1] NP group, and the signal intensities were gradually enhanced over time. ...
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Cell membrane- covered drug-delivery nanoplatforms have been garnering attention because of their enhanced bio-interfacing capabilities that originate from source cells. In this top-down technique, nanoparticles (NPs) are covered by various membrane coatings, including membranes from specialized cells or hybrid membranes that combine the capacities of different types of cell membranes. Here, hybrid membrane-coated doxorubicin (Dox)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (DPLGA@[RAW-4T1] NPs) were fabricated by fusing membrane components derived from RAW264.7(RAW) and 4T1 cells (4T1). These NPs were used to treat lung metastases originating from breast cancer. This study indicates that the coupling of NPs with a hybrid membrane derived from macrophage and cancer cells has several advantages, such as the tendency to accumulate at sites of inflammation, ability to target specific metastasis, homogenous tumor targeting abilities in vitro, and markedly enhanced multi-target capability in a lung metastasis model in vivo. The DPLGA@[RAW-4T1] NPs exhibited excellent chemotherapeutic potential with approximately 88.9% anti-metastasis efficacy following treatment of breast cancer-derived lung metastases. These NPs were robust and displayed the multi-targeting abilities of hybrid membranes. This study provides a promising biomimetic nanoplatform for effective treatment of breast cancer metastasis.
... However, a combination of both could provide insights on both the pathological phenomena and soft tissue anatomy to improve MR cancer imaging for stage detection, early diagnosis, and vascular imaging [59]. Therefore, many studies have turned to the design of encapsulating dual-modal MRI contrast agents in different formulations of liposomes and other nanocarriers [44,[60][61][62][63][64][65][66][67][68]. For example, Bos and coworkers [44] have shown the encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles and Gd-chelate (ProHance) in liposomes for dual modal MRI. ...
... They have demonstrated in vivo HIFU treatment and discussed corresponding relaxation parameter changes. Other studies include different formulation of dual-modal MR contrast agents, such as synthesis of gadolinium and iron oxideconjugated nanoparticles [61], surface functionalization of SPIO-encapsulated liposome with gadolinium chelates [64,67], size-controlled iron oxide nanoparticles [63] etc. Novel nanoparticle formulations with iron and manganese were developed for dual modal imaging and future theranostic purposes [68]. ...
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Rationale: Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. In this setting, real-time monitoring of therapy and tumor site would give the clinicians a handle to observe therapeutic response and to quantify drug amount to optimize the treatment. In this work, we developed a liposome-based cargo (cancer drugs) delivery strategy that could simultaneously monitor the real-time alternating magnetic field-induced cargo release from the change in MRI relaxation parameter R1 and the location and condition of liposome from the change in R2. The tumor site can then be monitored during the cargo release because liposomes would passively target the tumor site through the enhanced permeability and retention (EPR) effect. Physical insights from the experimental results and corresponding Monte Carlo spin dynamics simulations were also discussed. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles, diethylenetriaminepentaacetic acid gadolinium(III) (Gd(III)-DTPA), and a model cancer drug (fluorescein) were co-loaded in PEGylated thermosensitive liposomes. The liposomes were characterized by transmission electron cryo-microscopy (cryoTEM), dynamic light scattering (DLS), and inductively coupled plasma optical emission spectrometry (ICP-OES). Alternating magnetic field (AMF) was used to create controlled mild hyperthermia (39-42°C) and facilitate controlled cargo (fluorescein) release from the thermosensitive liposomes. MRI relaxation parameters, R1 and R2, were measured at room temperature. The temporal variation in R1 was used to obtain the temporal profile of cargo release. Due to their similar sizes, both the gadolinium and cargo (model cancer drug fluorescein) would come out of the liposomes together as a result of heating. The temporal variation in R2 was used to monitor SPIO nanoparticles to enhance the tumor contrast. Monte Carlo spin dynamics simulations were performed by solving the Bloch equations and modeling SPIO nanoparticles as magnetized impenetrable spheres. Results: TEM images and DLS measurements showed the diameter of the liposome nanoparticle ~ 200 nm. AMF heating showed effective release of the model drug. It was found that R1 increased linearly by about 70% and then saturated as the cargo release process was completed, while R2 remained approximately constant with an initial 7%-drop and then recovered. The linear increase in R1 is consistent with the expected linear cargo release with time upon AMF heating. Monte Carlo spin dynamics simulations suggest that the initial temporal fluctuation of R2 is due to the plausible changes of SPIO aggregation and the slow non-recoverable degradation of liposomal membrane that increases water permeability with time by the heating process. The simulations show an order of magnitude increase in R2 at higher water permeability. Conclusion: We have performed MR parameter study of the release of a cargo (model cancer drug, fluorescein) by magnetic heating from thermosensitive multifunctional liposomes loaded with dual contrast agents. The size of the liposome nanoparticles loaded with model cancer drug (fluorescein), gadolinium chelate, and SPIO nanoparticles was appropriate for a variety of cancer therapies. A careful and detailed analysis with theoretical explanation and simulation was carried out to investigate the correlation between MRI relaxation parameters, R1 and R2, and different cargo release fractions. We have quantified the cargo release using R1, which shows a linear relation between each other. This result provides a strong basis for the dosage control of drug delivered. On the other hand, the fairly stable R2 with almost constant value suggests that it could be used to monitor the position and condition of the liposomal site, as SPIO nanoparticles mostly remained in the aqueous core of the liposome. Because our synthesized SPIO-encapsulated liposomes could be targeted to tumor site passively by the EPR effect, or actively through magnetofection, this study provides a solid ground for developing MR cancer theranostics in combination of this nanostructure and AMF heating strategy. Furthermore, our simulation results predict a sharp increase in R2 during the AMF heating, which opens up the exciting possibility of high-resolution, high-contrast real-time imaging of the liposomal site during the drug release process, provided AMF heating could be incorporated into an MRI setup. Our use of the clinically approved materials, along with confirmation by theoretical simulations, make this technique a promising candidate for translational MR cancer theranostics.