Modifying Dendritic Cell Activation with Plasmonic Nano Vectors

Kieng Bao Vang,Ingrid Safina,Dmitry Nedosekin,Ganesh Kannarpady,Ruud P M Dings,Alexandru S Biris,Daniel Casciano,Vladimir P Zharov,Zeid A Nima,Waqar Majeed,Emilie Darrigues,Robert J Griffin,Fumiya Watanabe,Rajshekhar A Kore

doi:10.1038/s41598-017-04459-1

Abstract

Dendritic cells (DCs) can acquire, process, and present antigens to T-cells to induce an immune response. For this reason, targeting cancer antigens to DCs in order to cause an immune response against cancer is an emerging area of nanomedicine that has the potential to redefine the way certain cancers are treated. The use of plasmonically active silver-coated gold nanorods (henceforth referred to as plasmonic nano vectors (PNVs)) as potential carriers for DC tumor vaccines has not been presented before. Effective carriers must be able to be phagocytized by DCs, present low toxicity, and induce the maturation of DCs—an early indication of an immune response. When we treated DCs with the PNVs, we found that the cell viability of DCs was unaffected, up to 200 μg/ml. Additionally, the PNVs associated with the DCs as they were phagocytized and they were found to reside within intracellular compartments such as endosomes. More importantly, the PNVs were able to induce expression of surface markers indicative of DC activation and maturation, i.e. CD40, CD86, and MHC class II. These results provide the first evidence that PNVs are promising carriers for DC-based vaccines and warrant further investigating for clinical use.

Highlights

Dendritic cells (DCs) can acquire, process, and present antigens to T-cells to induce an immune response
We confirmed the size distribution of the plasmonic nano vectors (PNVs) by Atomic Force Microscope (AFM). Both height and phase images reveal that the PNVs were mostly uniform in size and that they corresponded to the aspect ratio (AR) = 3.0 ± 0.23 as previously described (Fig. 1d,e and Supplementary Fig. 1a–c)[30]
Because PNV treatment caused an increase in the expression of CD40 on the cell surface of DCs, we investigated whether other surface markers of maturation increased

Summary

Introduction

Dendritic cells (DCs) can acquire, process, and present antigens to T-cells to induce an immune response. The PNVs were able to induce expression of surface markers indicative of DC activation and maturation, i.e. CD40, CD86, and MHC class II. These results provide the first evidence that PNVs are promising carriers for DC-based vaccines and warrant further investigating for clinical use. In order to do this, DCs must be “educated” or “trained” so they can recognize the pathogen of question and start to initiate the process of an immune response This education process involves turning on, or, up-regulating cell surface receptors on the DCs. In general, DCs exist in two states: a resting state (immature phenotype) and an activated state (mature phenotype), with distinct cell surface receptor expression levels to indicate their specific state.

Methods

Results

Conclusion