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MR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma.

ABSTRACT: Cell-based drug delivery systems have shown promising capability for tumor-targeted therapy owing to the intrinsic tumor-homing and drug-carrying property of some living cells. However, imaging tracking of their migration and bio-effects is urgently needed for clinical application, especially for glioma. Here, we report the inflammation-activatable engineered neutrophils by internalizing doxorubicin-loaded magnetic mesoporous silica nanoparticles (ND-MMSNs) which can provide the potential for magnetic resonance (MR) imaging tracking of the drug-loaded cells to actively target inflamed brain tumor after surgical resection of primary tumor. The phagocytized D-MMSNs possess high drug loading efficiency and do not affect the host neutrophils' viability, thus remarkably improving intratumoral drug concentration and delaying relapse of surgically treated glioma. Our study offers a new strategy in targeted cancer theranostics through combining the merits of living cells and nanoparticle carriers.

SUBMITTER: Wu M

PROVIDER: S-EPMC6235838 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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MR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma.

Wu Meiying M Zhang Haixian H Tie Changjun C Yan Chunhong C Deng Zhiting Z Wan Qian Q Liu Xin X Yan Fei F Zheng Hairong H

Nature communications 20181114 1

Cell-based drug delivery systems have shown promising capability for tumor-targeted therapy owing to the intrinsic tumor-homing and drug-carrying property of some living cells. However, imaging tracking of their migration and bio-effects is urgently needed for clinical application, especially for glioma. Here, we report the inflammation-activatable engineered neutrophils by internalizing doxorubicin-loaded magnetic mesoporous silica nanoparticles (ND-MMSNs) which can provide the potential for ma ...[more]

PMID: 30429468

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Project description:PurposeTo determine the feasibility of T2-weighted magnetic resonance (MR) imaging in the noninvasive quantification of renal inflammation by using superparamagnetic iron oxide (SPIO) nanoparticles targeted to tissue-bound C3 activation fragments in a mouse model of lupus nephritis.Materials and methodsAll animal procedures were approved by the University of Colorado-Denver animal care and use committee. SPIO nanoparticles were encapsulated by using amine-functionalized phospholipids. A recombinant protein containing the C3d-binding region of complement receptor type 2 (CR2) was then conjugated to the surface of the SPIO nanoparticle. Five MRL/lpr mice (a model of lupus nephritis) and six C57BL/6 wild-type mice were assessed with T2-weighted MR imaging at baseline and after SPIO injection. The same five MRL/lpr mice and three C57BL/6 mice also underwent MR imaging after injection of CR2-targeted SPIO. A series of T2-weighted pulses with 16 echo times was used to enable precise T2 mapping and calculation of T2 relaxation times in the cortex and outer and inner medulla of the kidneys, as well as in the spleen, muscle, and fat. The effects of treatment and animal genotype on T2 relaxation times were analyzed with repeated-measures analysis of variance.ResultsAt baseline, the T2-weighted signal intensity in the kidneys of MRL/lpr mice was higher than that in the kidneys of wild-type mice. Injection of untargeted SPIO did not alter the T2-weighted signal in the kidneys in either strain of mice. Injection of CR2-targeted SPIO in MRL/lpr mice, however, caused a significant accumulation of targeted iron oxide with a subsequent decrease in T2 relaxation times in the cortex and outer and inner medulla of the kidneys. No changes in T2 relaxation time were observed in the wild-type mice after injection of targeted SPIO.ConclusionInjection of CR2-conjugated SPIO caused a significant reduction in T2-weighted MR imaging signal and T2 relaxation time in nephritic kidneys.

Project description:Background and purposeBlood oxygenation level-dependent MR imaging is increasingly used clinically to noninvasively assess cerebrovascular reactivity and/or language and motor function. However, many patients have metallic implants, which will induce susceptibility artifacts, rendering the functional information uninformative. Here, we calculate and interpret blood oxygenation level-dependent MR imaging artifact impact arising from surgically implanted hardware.Materials and methodsA retrospective analysis of all blood oxygenation level-dependent MRIs (n = 343; B0 = 3T; TE = 35 ms; gradient echo EPI) acquired clinically (year range = 2006-2014) at our hospital was performed. Blood oxygenation level-dependent MRIs were most commonly prescribed for patients with cerebrovascular disease (n = 80) or patients undergoing language or motor localization (n = 263). Artifact volume (cubic centimeters) and its impact on clinical interpretation were determined by a board-certified neuroradiologist.ResultsMean artifact volume associated with intracranial hardware was 4.3 ± 3.2 cm(3) (range = 1.1-9.4 cm(3)). The mean artifact volume from extracranial hardware in patients with cerebrovascular disease was 28.4 ± 14.0 cm(3) (range = 6.1-61.7 cm(3)), and in patients with noncerebrovascular disease undergoing visual or motor functional mapping, it was 39.9 (3)± 27.0 cm(3) (range = 6.9-77.1 cm(3)). The mean artifact volume for ventriculoperitoneal shunts was 95.7 ± 39.3 cm(3) (range = 64.0-139.6 cm(3)). Artifacts had no-to-mild effects on clinical interpretability in all patients with intracranial implants. Extracranial hardware artifacts had no-to-moderate impact on clinical interpretability, with the exception of 1 patient with 12 KLS-Martin maxDrive screws with severe artifacts precluding clinical interpretation. All examined ventriculoperitoneal shunts resulted in moderate-to-severe artifacts, limiting clinical interpretation.ConclusionsBlood oxygenation level-dependent MR imaging yields interpretable functional maps in most patients beyond a small (30-40 cm(3)) artifact surrounding the hardware. Exceptions were ventriculoperitoneal shunts, particularly those with programmable valves and siphon gauges, and large numbers of KLS-Martin maxDrive screws.

Dataset Information

MR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma.

Publications

MR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma.

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