Cell sorting microbeads as novel contrast agent for magnetic resonance imaging

Abstract

The success of several cell-based therapies and prevalent use of magnetic resonance imaging (MRI) in the clinic has fueled the development of contrast agents for specific cell tracking applications. Safe and efficient labeling of non-phagocytic cell types such as T cells nonetheless remains challenging. We developed a one-stop shop approach where the T cell sorting agent also labels the cells which can subsequently be depicted using non-invasive MRI. We compared the MR signal effects of magnetic-assisted cell sorting microbeads (CD25) to the current preclinical gold standard, ferumoxytol. We investigated in vitro labeling efficiency of regulatory T cells (Tregs) with MRI and histopathologic confirmation. Thereafter, Tregs and T cells were labeled with CD25 microbeads in vitro and delivered via intravenous injection. Liver MRIs pre- and 24 h post-injection were performed to determine in vivo tracking feasibility. We show that CD25 microbeads exhibit T2 signal decay properties similar to other iron oxide contrast agents. CD25 microbeads are readily internalized by Tregs and can be detected by non-invasive MRI with dose dependent T2 signal suppression. Systemically injected labeled Tregs can be detected in the liver 24 h post-injection, contrary to T cell control. Our CD25 microbead-based labeling method is an effective tool for Treg tagging, yielding detectable MR signal change in cell phantoms and in vivo. This novel cellular tracking method will be key in tracking the fate of Tregs in inflammatory pathologies and solid organ transplantation.

Multi-Armed Anti-CD40-Mediated Dual Drug Delivery System Based on Mesoporous Silica/Au Nanorod Nanocomposites for Multimodality Imaging and Combination Therapy

“…The in vitro FL imaging of anti-CD40-gated nanocomposites was studied in MCF-7 (CD40 negative) and A549 cells (CD40 positive) by CLSM. As shown in CLSM images (Figure 3E), the FL intensity of CPT increased obviously with incubation times (3,6,12, and 24 h), indicating the cellular uptake and CPT release of anti-CD40-gated DOTV−cGNR@MSNs within A549 and MCF-7 cells. Due to the acidic microenvironment of both tumor cells, the acylhydrazone bonds modified on the nanovehicles were cleaved to open the anti-CD40 nanogate, giving rise to CPT FL signals after its release.…”

“…In recent years, nanomedicine has incorporated new features of nanodevices, such as photothermal effect, 1,2 persistent luminescence (PL), 3,4 and magnetic resonance imaging (MRI), 5,6 showing great advantages in various biomedical applications. 7−9 In particular, the core−shell nanoparticles and transition-metal oxide-doped materials exploited combination properties of nanocomposites (NPs) for medical diagnosis and treatment, which are especially useful in drug delivery systems, combination therapy, and medical imaging.…”

“…MCF-7 and A549 cells were seeded and cultured in confocal culture dishes. The anti-CD40-gated DOTV−cGNR@MSNs with CPT loading (100 μg/mL) were added into the dishes, and the intracellular drug release behaviors after different incubation times (3,6,12, and 24 h) were observed by CLSM, which acquired CLSM images in the optical window of CPT (λ ex = 365 nm, blue). For NIR-triggered drug release, the anti-CD40-gated DOTV−cGNR@MSNs with CPT loading (100 μg/mL) were added to the A549 and MCF-7 cells, respectively.…”

“…In recent years, nanomedicine has incorporated new features of nanodevices, such as photothermal effect, , persistent luminescence (PL), , and magnetic resonance imaging (MRI), , showing great advantages in various biomedical applications. − In particular, the core–shell nanoparticles and transition-metal oxide-doped materials exploited combination properties of nanocomposites (NPs) for medical diagnosis and treatment, which are especially useful in drug delivery systems, combination therapy, and medical imaging. − Moreover, the development of nanocomposite-based stimuli-responsive drug delivery systems that are able to deliver small-molecule and biomacromolecule drugs can precisely control the cargo release behaviors and greatly improve therapeutic effects. − …”