Synthesis of Multifunctional Fe₃O₄–CdSe/ZnS Nanoclusters Coated with Lipid A toward Dendritic Cell-Based Immunotherapy

Abstract

We demonstrate a novel route to synthesize Fe3O4-CdSe/ZnS multifunctional nanoclusters (MNCs) with excellent optical and magnetic properties and biocompatibility. The successful fabrication of highly fluorescent and magnetic MNCs is achieved via a coupling process based on a partial ligand exchange reaction at the aqueous-organic solution interface. In addition, we show that dendritic cells (DCs), the sentinel of the immune system, can uptake the MNCs without significant change in cell viability. The MNCs uptaken by the DCs can be used for imaging, tracking, and separating the DCs. Furthermore, the MNCs can be loaded with a pathogen-associated molecular pattern, lipid A, via a hydrophobic-hydrophobic interaction. Ex vivo labeling of DCs with the MNC-lipid A complex enhances the DC migration to draining lymph nodes and tumor antigen-specific T cell responses in vivo. Our work may contribute to the development of synthetic routes to various multifunctional nanoclusters and DC-based cancer immunotherapies.

Iron Metabolism in Cancer

“…A novel combined use of IONP (superparamagnetic Fe 3 O 4 nanoparticles) as a vaccine delivery platform and immune potentiator greatly promotes immune cells activation and cytokines production, stimulating potent cellular immune responses, and antigen specific CTL responses [188,194]. Macrophages and DC cells, functioning as the most professional antigen presenting cells, can be activated by Fe 3 O 4 -OVA nanoparticles and release diverse pro-inflammatory cytokines—including IL-6, interferon (IFN)-γ, and TNF-α in vitro—thus causing more potent immune responses [195,196]. Another evidence shows that IONP can strongly inhibit the biosynthesis metabolism of macrophages [197].…”

Metallic Nanoclusters for Cancer Imaging and Therapy

“…As an example, multifunctional clusters (MNCs) Fe 3 O 4 -CdSe/ZnS (Fig. 6C) were synthesized by Kim et al [133] and displayed excellent magnetic and optical properties and biocompatibility. MNCs-lipid A was prepared by loading lipid A onto MNCs to enhance the migration of dendritic cells (DC) and antigen-specific T cell responses to tumor in vivo.…”

Preparation of ellipsoid-shaped supraparticles with modular compositions and investigation of shape-dependent cell-uptake

“…4 Of special interest is the combination of different nanoparticle types with selected properties into hybrid SPs to unite different properties in one nanostructure. Depending on the properties of the nanoparticle building blocks, possible applications of SPs range from the biomedical field [5][6][7] to optics 8 and heterogeneous catalysis 9 . For example, fluorescence and superparamagnetism combined in one SP could be employed for multi-modal imaging.…”