HSA coated MnO nanoparticles with prominent MRI contrast for tumor imaging

Huang, Jing; Xie, Jin; Chen, Kai; Bu, Lihong; Lee, Seulki; Cheng, Zhen; Li, Xingguo; Chen, Xiaoyuan

doi:10.1039/c0cc01041c

Cited by 129 publications

(112 citation statements)

References 20 publications

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“…2a) is obtained by measuring the relaxation rate of water protons with increasing concentrations of NPs, and is calculated to be 8.26 mM −1 s −1 . This value is twice higher than that of Gd-DTPA (4.11 mM −1 s −1 ) and the highest value reported to date for Mn-based NPs (Table 1)2324424344454647. These nanocrystals are also tested in PBS solution in order to simulate the culture medium.…”

Section: Resultsmentioning

confidence: 87%

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging

Xiao

Tian

Yang

et al. 2013

Sci Rep

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Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic resonance imaging due to the impressive contrast ability. However, the reported Mn-based NPs possess low relaxivity and there are no immunotoxicity data regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh relaxivity of water protons of 8.26 mM−1s−1 from the Mn3O4 NPs synthesized by a simple and green technique, which is twice higher than that of commercial gadolinium (Gd)-based contrast agents (4.11 mM−1s−1) and the highest value reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4 NPs biocompatibilities both in vitro and in vivo are satisfactory based on systematical studies of the intrinsic toxicity including cell viability of human nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in cells and in vivo immunotoxicity. These findings pave the way for the practical clinical diagnosis of Mn based NPs as safe probes for in vivo imaging.

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Section: Resultsmentioning

confidence: 87%

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging

Xiao

Tian

Yang

et al. 2013

Sci Rep

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“…The massive uptake by the liver was evidenced in the PET data, as soon as one hour aer injection. 55 These results indicated that MnO particles, as many other inorganic core nanoparticles in that size range, are strongly sequestrated by the RES if they are not adequately coated with molecules preventing or delaying their opsonisation. RES-sequestrated nanoparticles are more susceptible to remain in the organism for longer periods, which, in the case of Mn 2+ -containing nanoparticles, would represent a toxicological risk.…”

Section: Manganese Biodistribution Studymentioning

confidence: 95%

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

et al. 2014

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A majority of MRI procedures requiring intravascular injections of contrast agents are performed with paramagnetic chelates. Such products induce vascular signal enhancement and they are rapidly excreted by the kidneys. Unfortunately, each chelate is made of only one paramagnetic ion, which, taken individually, has a limited impact on the MRI signal. In fact, the detection of molecular events in the nanomolar range using T 1 -weighted MRI sequences requires the design of ultra-small particles containing hundreds of paramagnetic ions per contrast agent unit. Ultra-small nanoparticles of manganese oxide (MnO, 6-8 nm diameter) have been developed and proposed as an efficient and at least 1000Â more sensitive "positive" MRI contrast agent. However no evidence has been found until now that an adequate surface treatment of these particles could maintain their strong blood signal enhancement, while allowing their rapid and efficient excretion by the kidneys or by the hepatobiliairy pathway. Indeed, the sequestration of MnO particles by the reticuloendothelial system followed by strong uptake in the liver and in the spleen could potentially lead to Mn 2+ -induced toxicity effects. For ultra-small MnO particles to be applied in the clinics, it is necessary to develop coatings that also enable their efficient excretion within hours. This study demonstrates for the first time the possibility to use MnO particles as T 1 vascular contrast agents, while enabling the excretion of >70% of all the Mn injected doses after 48 h. For this, small, biocompatible and highly hydrophilic pegylated bis-phosphonate dendrons (PDns) were grafted on MnO particles to confer colloidal stability, relaxometric performance, and fast excretion capacity. The chemical and colloidal stability of MnO@PDn particles were confirmed by XPS, FTIR and DLS. The relaxometric performance of MnO@PDns as "positive" MRI contrast agents was assessed (r 1 ¼ 4.4 mM À1 s À1 , r 2 /r 1 ¼ 8.6; 1.41 T and 37 C). Mice were injected with 1.21 mg Mn per kg (22 mmol Mn per kg), and scanned in MRI up to 48 h.The concentration of Mn in key organs was precisely measured by neutron activation analysis and confirmed, with MRI, the possibility to avoid RES nanoparticle sequestration through the use of phosphonate dendrons. Due to the fast kidney and hepatobiliairy clearance of MnO particles conferred by PDns, MnO nanoparticles can now be considered for promising applications in T 1 -weighted MRI applications requiring less toxic although highly sensitive "positive" molecular contrast agents.

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“…6,7 Therefore, attention has shifted to alternative agents such as manganese (Mn)-based complexes [8][9][10][11] and nanoparticles (NPs), [12][13][14][15] which has produced encouraging results for both in vitro and in vivo MR imaging of cancer. [16][17][18] For instance, MnO NPs have been successfully used for T 1 -weighted MR imaging of metastatic brain tumors. 19 However, compared with gadolinium-based contrast agent, [20][21][22][23] most of the Mn-based NPs exhibit relatively low r 1 relaxivity, 24 which may limit their uses in sensitive T 1 -weighted MR imaging of tiny gliomas.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Gadolinium-Doped Manganese Carbonate Nanoparticles for Targeted MR/Fluorescence Imaging of Tiny Brain Gliomas

Shao

et al. 2015

Anal. Chem.

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Manganese (Mn)-based nanoparticles have been proved to be promising MR T1 contrast agents for the diagnosis of brain tumors. However, most of them exhibit a low relaxation rate, resulting in an insufficient enhancement effect on tiny gliomas. Herein, we developed gadolinium (Gd)-doped MnCO3 nanoparticles with a size of 11 nm via the thermal decomposition of Mn-oleate in the presence of Gd-oleate. Owing to the small size and Gd doping, these Gd-doped MnCO3 NPs, when endowed with excellent aqueous dispersibility and colloidal stability, exhibited a high r1 relaxivity of 6.81 mM(-1) s(-1). Moreover, the Gd/MnCO3 NPs were used as a reliable platform to construct a glioma-targeted MR/fluorescence bimodal nanoprobe. The high relaxivity, the bimodal imaging capability, and the specificity nominate the multifunctional Gd doped MnCO3 NPs as an effective nanoprobe for the diagnostic imaging of tiny brain gliomas with an improved efficacy.

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HSA coated MnO nanoparticles with prominent MRI contrast for tumor imaging

Cited by 129 publications

References 20 publications

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

Multifunctional Gadolinium-Doped Manganese Carbonate Nanoparticles for Targeted MR/Fluorescence Imaging of Tiny Brain Gliomas

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