Multimodal imaging of dendritic cells using a novel hybrid magneto-optical nanoprobe.

A transfecting agent-coated hybrid imaging nanoprobe (HINP) composed of visible and near-infrared (NIR) light emitting quantum dots (QDs) tethered to superparamagnetic iron oxide (SPIO) nanoparticles was developed. The surface modification of QDs and SPIO particles and incorporation of dual QDs within the SPIO were characterized by dynamic light scattering (DLS), quartz crystal microbalance (QCM) analysis and atomic force microscopy (AFM). The optical contrasting properties of HINP were characterized by absorption and photoluminescence spectroscopy and fluorescence imaging. Multicolor HINP was used in imaging the migration of dendritic cells (DCs) by optical, two-photon and magnetic resonance imaging techniques. FROM THE CLINICAL EDITOR: The development of a transfecting agent-coated hybrid imaging nanoprobe (HINP) composed of visible and near-infrared light emitting quantum dots (QDs) tethered to superparamagnetic iron oxide nanoparticles is reported in this paper. Multicolor HINP was used in imaging the migration of dendritic cells by optical, two-photon and magnetic resonance imaging techniques.

Magnetic nanoparticles for imaging dendritic cells.

We report the development of superparamagnetic iron oxide (SPIOs) nanoparticles and investigate the migration of SPIO-labeled dendritic cells (DCs) in a syngeneic mouse model using magnetic resonance (MR) imaging. The size of the dextran-coated SPIO is roughly 30 nm, and the DCs are capable of independent uptake of these particles, although not at levels comparable to particle uptake in the presence of a transfecting reagent. On average, with the assistance of polylysine, the particles were efficiently delivered inside DCs within one hour of incubation. The SPIO particles occupy approximately 0.35% of cell surface and are equivalent to 34.6 pg of iron per cell. In vivo imaging demonstrated that the labeled cells migrated from the injection site in the footpad to the corresponding popliteal lymph node. The homing of labeled cells in the lymph nodes resulted in a signal drop of up to 79%. Furthermore, labeling DCs with SPIO particles did not compromise cell function, we demonstrated that SPIO-enhanced MR imaging can be used to track the migration of DCs effectively in vivo.

MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells.

Exosomes are 50-90 nm vesicles with antigen presenting ability carrying major histocompatibility complex (MHC) class I, class II, abundant co-stimulatory molecules and some tetraspan proteins. Although dendritic cells (DCs) are one of the professional antigen presenting cells capable of presenting exogenous antigens in MHC class I-mediated antigen specific manner (cross-presentation), the cross-presentation ability by exosomes from immature or mature DCs are unknown. Here we show that exosomes released from ovalbumin (OVA) protein-pulsed bone marrow derived dendritic cells (BM-DCs) weakly present the peptide determinants to OVA specific MHC class I-restricted CD8(+) T cell hybridomas. The exosomes secreted by OVA(257-264) peptide- or OVA protein-pulsed mature BM-DCs activated OVA specific MHC class I-restricted T cell hybridomas more efficiently than those from immature BM-DCs. Transporters associated with antigen processing (TAP) deficient mice-derived BM-DCs were also used to examine whether functional TAP activity was required for cross-presentation by exosomes. The exosomes obtained from OVA(257-264) peptide-pulsed BM-DCs derived from TAP(-/-) mice showed a significant antigen presenting ability to OVA specific MHC class I-restricted T cell hybridomas. Altogether, our data indicate that BM-DCs secrete exosomes with weak cross-presentation ability.

Induction of antitumor immunity by dendritic cells loaded with membrane-translocating mucin 1 Peptide antigen.

To investigate the role of enhanced antigen presentation in dendritic cell (DC)-based immunotherapy. Here, we describe the development of a cell-penetrating mucin 1 (MUC1) antigen and its immunotherapeutic potential against tumors. After animal groups received two immunizations of MUC1-MPA(11)P-pulsed DCs, we observed a marked tumor regression compared with the mice treated with DCs alone or DCs pulsed with MUC1 peptide. We confirmed the migration and homing of DCs in the popliteal lymph node using magnetic resonance imaging during the study. In summary, enhanced antigen uptake using an MPA(11)P delivery molecule improves cell therapy.

Dendritic cells: therapy and imaging.

BACKGROUND: Dendritic cells (DCs) play a major role in cell-mediated immunotherapy. In this approach, DCs are isolated from cancer patients and pulsed with exogenous and specific tumor antigens in vitro, and the antigen-loaded DCs are then transferred to the hosts to enhance the immune response against tumor targets. Clinical observations and animal studies have shown that tumors can elicit immune responses caused by tumor infiltration of T-lymphocytes. Several pilot clinical trials have been recently conducted using this strategy for treating several types of cancers. OBJECTIVE: To optimize DC-based therapy with emerging molecular imaging techniques. METHODS: A review of the most current literature on DCs and imaging work. RESULTS/CONCLUSION: The translational application of DC-based therapy can be supported greatly through molecular imaging. New discoveries on DC migration and behavior in vivo will lead to new advances in the treatment of a broad range of cancers.