Yolk–shell magnetic composite Fe3O4@Co/Zn-ZIF for MR imaging-guided chemotherapy of tumors in vivo

According to the differences of microenvironments between tumors and healthy tissues, if the anticancer drugs or magnetic resonance contrast agents (MRCAs) can be controlled to precisely match physiological needs at targeted tumor sites, it is expected to acquire better therapeutic efficacy and more accurate diagnosis. Over the decade, stimuli-responsive nanomaterials have been a research hotspot for cancer treatment and diagnosis because they show many excellent functions, such as in vivo imaging, combined targeting drug delivery and systemic controlled release, extended circulation time, etc. Among the various stimuli nanosystems, pH-stimuli mode is regarded as the most general strategy because of solid tumors acidosis. When exposed to weakly acidic tumor microenvironment, pH-responsive nanoplatforms can generate physicochemical changes for their structure and surface characteristics, causing drug release or contrast enhancement. In this review, we focused on the designs of various pH-responsive nanoplatforms and discussed the mechanisms of controlled drug release or switch on-off in MRCAs. This review also discussed the efficacy of cellular internalization for these nanoplatforms via endocytosis of acidic tumor cell. Meanwhile, nanoplatforms response to acidic intracellular pH (such as endosome, lysosome) are discussed, along with approaches for improving drug release performance and magnetic resonance contrast enhancement. A greater understanding of these pH-responsive nanoplatforms will help design more efficient nanomedicine to address the challenges encountered in conventional diagnosis and chemotherapy.

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In vivo Monitoring of Oxygen Levels in Human Brain Tumor Between Fractionated Radiotherapy Using Oxygen-enhanced MR Imaging

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405614666180925144814 ◽

2020 ◽

Vol 16 (4) ◽

pp. 427-432

Author(s):

Junchao Qian ◽

Xiang Yu ◽

Bingbing Li ◽

Zhenle Fei ◽

Xiang Huang ◽

...

Keyword(s):

Mr Imaging ◽

Tumor Cells ◽

Normal Tissue ◽

Oxygen Level ◽

Tissue Oxygen ◽

Human Brain Tumor ◽

Fractionated Radiotherapy ◽

Oxygen Levels ◽

Oxygen Breathing

Background:: It was known that the response of tumor cells to radiation is closely related to tissue oxygen level and fractionated radiotherapy allows reoxygenation of hypoxic tumor cells. Non-invasive mapping of tissue oxygen level may hold great importance in clinic. Objective: The aim of this study is to evaluate the role of oxygen-enhanced MR imaging in the detection of tissue oxygen levels between fractionated radiotherapy. Methods: A cohort of 10 patients with brain metastasis was recruited. Quantitative oxygen enhanced MR imaging was performed prior to, 30 minutes and 22 hours after first fractionated radiotherapy. Results: The ΔR1 (the difference of longitudinal relaxivity between 100% oxygen breathing and air breathing) increased in the ipsilateral tumor site and normal tissue by 242% and 152%, respectively, 30 minutes after first fractionated radiation compared to pre-radiation levels. Significant recovery of ΔR1 in the contralateral normal tissue (p < 0.05) was observed 22 hours compared to 30 minutes after radiation levels. Conclusion: R1-based oxygen-enhanced MR imaging may provide a sensitive endogenous marker for oxygen changes in the brain tissue between fractionated radiotherapy.

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Assessment of Ploy Dopamine Coated Fe3O4 Nanoparticles for Melanoma (B16-F10 and A-375) Cells Detection

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200513084616 ◽

2020 ◽

Vol 20 (16) ◽

pp. 1918-1926

Author(s):

Fahimeh H. Beigi ◽

Soheil Fatahian ◽

Sogand Shahbazi-Gahrouei ◽

Daryoush Shahbazi-Gahrouei ◽

Amin Farzadniya

Keyword(s):

Mr Imaging ◽

Mtt Assay ◽

Fe3o4 Nanoparticles ◽

Normal Skin ◽

Iron Concentration ◽

Positive Effects ◽

Skin Cells ◽

Melanoma B16 ◽

Co Precipitation

Objective: Polydopamine coated iron oxide nanoparticles (Fe3O4@PDA NPs) were synthesized, characterized, and their MR imaging contrast agents and photothermal potency were evaluated on melanoma (B16-F10 and A-375) cells and normal skin cells. To this end, MTT assay, Fe concentration, and MR imaging of both coated and uncoated NPs were assessed in C57BL/6 mice. Methods: Fe3O4 nanoparticles were synthesized using co-precipitation, and coated with polydopamine. The cytotoxicity of Fe3O4 and Fe3O4@PDA NPs on melanoma cells, with different concentrations, were obtained using MTT assay. MR images and Fe concentrations of nanoprobe and nanoparticles were evaluated under in vivo conditions. Results: Findings indicated that uncoated Fe3O4 showed the highest toxicity in animal (B16-F10) cells at 450μg/ml after 72h, while the highest toxicity in human (A-375) cells were observed at 350μg/ml. These nanoparticles did not reveal any cytotoxicity to normal skin cells, despite having some toxicity features in A-375 cells. MR image signals in the tumor were low compared with other tissues. The iron concentration in the tumor was higher than that of other organs. Conclusion: It is concluded that the cytotoxicity of Fe3O4@PDA was found to be significantly lower than uncoated nanoparticles (p <0.001), which allows some positive effects on reducing toxicity. The prepared nanoprobe may be used as a contrast agent in MR imaging.

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The role of cochlear implant positioning on MR imaging quality: a preclinical in vivo study with a novel implant magnet system

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-021-07005-y ◽

2021 ◽

Author(s):

Pietro Canzi ◽

Marianna Magnetto ◽

Anna Simoncelli ◽

Marco Manfrin ◽

Federico Aprile ◽

...

Keyword(s):

Mr Imaging ◽

Cochlear Implant ◽

Occipital Lobe ◽

Brain Structures ◽

Magnet System ◽

High Positive Correlation ◽

Imaging Quality ◽

Signal Void ◽

Mri Surveillance

Abstract Purposes To investigate the effects for Ultra 3D cochlear implant (CI) positioning on MR imaging quality, looking at a comprehensive description of intracranial structures in cases of unilateral and bilateral CI placement. Methods Four CI angular positions (90°, 120°, 135° and 160°) at 9 cm distance from the outer-ear canal were explored. The 1.5 T MRI assessment included our institutional protocol for the investigation of brain pathologies without gadolinium application. Three investigators (two experienced neuroradiologists and one experienced otoneurosurgeon) independently evaluated the MR findings. A 4-point scale was adopted to describe 14 intracranial structures and to determine which CI positioning allowed the best image quality score and how bilateral CI placement modified MRI scan visibility. Results A high positive correlation was found between the three blinded observers. Structures situated contralateral from the CI showed high-quality values in all four placements. Structures situated ipsilaterally provided results suitable for diagnostic purposes for at least one position. At 90°, artifacts mainly involved brain structures located cranially and anteriorly (e.g., temporal lobe); on the contrary, at 160°, artifacts mostly influenced the posterior fossa structures (e.g., occipital lobe). For the bilateral CI condition, MR imaging examination revealed additional artifacts involving all structures located close to either CI, where there was a signal void/distortion area. Conclusions Suitable unilateral CI positioning can allow the visualization of intracranial structures with sufficient visibility for diagnostic purposes. Bilateral CI positioning significantly deteriorates the anatomical visibility. CI positioning might play a crucial role for patients who need post-operative MRI surveillance.

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GMP-compliant fully automated radiosynthesis of [18F]FEPPA for PET/MRI imaging of regional brain TSPO expression

EJNMMI Research ◽

10.1186/s13550-021-00768-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chi-Wei Chang ◽

Chuang-Hsin Chiu ◽

Ming-Hsien Lin ◽

Hung-Ming Wu ◽

Tsung-Hsun Yu ◽

...

Keyword(s):

Mr Imaging ◽

Western Blotting ◽

Second Generation ◽

Mrna Levels ◽

Automated Radiosynthesis ◽

Lps Challenge ◽

Tnf Α ◽

The Brain ◽

Tspo Expression

Abstract Background Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p < 0.05) and Iba-1 (p < 0.01) were upregulated in the brain after LPS administration. In LPS-injected mice, TSPO immunoactivity colocalized with Iba-1 in the cerebrum and TSPO was significantly overexpressed in the hippocampus and cerebellum. The peripheral organs (heart, lung) of LPS-injected mice had higher [18F]FEPPA signal-to-noise ratios than control mice. Conclusions Based on the current data on ligand specificity and selectivity in central tissues using 7 T PET/MR imaging, we demonstrate that [18F]FEPPA accumulations significant increased in the specific brain regions of systemic LPS-induced neuroinflammation (5 mg/kg). Future investigations are needed to determine the sensitivity of [18F]FEPPA as a biomarker of neuroinflammation as well as the correlation between the PET signal intensity and the expression levels of TSPO.

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Real time monitoring of peptide delivery in vitro using high payload pH responsive nanogels

Polymer Chemistry ◽

10.1039/c9py01120j ◽

2020 ◽

Vol 11 (2) ◽

pp. 425-432 ◽

Cited By ~ 2

Author(s):

Shegufta Farazi ◽

Fan Chen ◽

Henry Foster ◽

Raelene Boquiren ◽

Shelli R. McAlpine ◽

...

Keyword(s):

Real Time ◽

Intracellular Delivery ◽

Peptide Delivery ◽

High Loading ◽

Loading Capacity ◽

Ph Responsive ◽

Real Time Monitoring ◽

High Payload

A pH responsive pMAA nanogel that demonstrates high loading capacity and rapid intracellular delivery of hydrophilic peptides.

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