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A dual-modal PET/near infrared fluorescent nanotag for long-term immune cell tracking.

ABSTRACT: Adoptive cell transfer of targeted chimeric antigen receptor (CAR) T cells has emerged as a highly promising cancer therapy. The pharmacodynamic action or CAR T cells is closely related to their pharmacokinetic profile; because of this as well as the risk of non-specific action, it is important to monitor their biodistribution and fate following infusion. To this end, we developed a dual-modal PET/near infrared fluorescent (NIRF) nanoparticle-based imaging agent for non-genomic labeling of human CAR T cells. Since the PET/NIRF nanoparticles did not affect cell viability or cytotoxic functionality and enabled long-term whole-body CAR T cell tracking using PET and NIRF in an ovarian peritoneal carcinomatosis model, this platform is a viable imaging technology to be applied in other cancer models.

SUBMITTER: Harmsen S

PROVIDER: S-EPMC7870530 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Amyloid-? (A?) peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer's disease (AD) and is related to the pathogenesis of AD. Passive anti-A? immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific anti-A? monoclonal antibodies (aA?mAbs) to delay A? aggregation in the brain. However, the main disadvantage of this approach is the required readministration of the aA?mAbs at frequent intervals. There are only a few reports describing in vitro study for the immobilization of aA?mAbs to nanoparticles as potential targeting agents of A? aggregates. In this article, we report the immobilization of the aA?mAb clone BAM10 to near-infrared fluorescent maghemite nanoparticles for the inhibition of A?40 fibrillation kinetics and the specific detection of A?40 fibrils. The BAM10-conjugated iron oxide nanoparticles were well-characterized, including their immunogold labeling and cytotoxic effect on PC-12 (pheochromocytoma cell line). Indeed, these antibody-conjugated nanoparticles significantly inhibit the A?40 fibrillation kinetics compared with the same concentration, or even five times higher, of the free BAM10. This inhibitory effect was confirmed by different assays such as the photo-induced crosslinking of unmodified proteins combined with sodium dodecyl sulfate- polyacrylamide gel electrophoresis. A cell viability assay also confirmed that these antibody-conjugated nanoparticles significantly reduced the A?40-induced cytotoxicity to PC-12 cells. Furthermore, the selective labeling of the A?40 fibrils with the BAM10-conjugated near-infrared fluorescent iron oxide nanoparticles enabled specific detection of A?40 fibrils ex vivo by both magnetic resonance imaging and fluorescence imaging. This study highlights the immobilization of the aA?mAb to dual-modal nanoparticles as a potential approach for aA?mAb delivery, eliminating the issue of readministration, and contributes to the development of multifunctional agents for diagnosis and therapy of AD.

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A dual-modal PET/near infrared fluorescent nanotag for long-term immune cell tracking.

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