The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model.

Changqiang Wu,Rongrong Jin,Wencheng Zhu,Hua Ai,Ye Xu

doi:10.3389/fonc.2020.621642

Abstract

Dendritic cell (DC) vaccines have recently been developed for the treatment of various cancers but often do not function as well as expected, primarily due to the highly complex in vivo immune environment. This proof-of-principle study aimed to test the feasibility of modulating the in vivo behaviors of DC vaccines (DCVs) by introducing siRNA-laden magnetic resonance (MR) imaging nanovectors into cells, while providing visible information on their homing to lymph nodes. The N-alkyl-PEI2k-LAC/SPIO nanocomposites were prepared and characterized, showing favorable properties of siRNA transfection and MRI labeling efficiency in DCs. Cell viability assays revealed no observable effects on the survival and phenotype of DCs if the concentration of the complex was within 8 μg Fe/ml. An orthotopic mouse model of breast cancer was developed. The DCVs transfected with IDO siRNA contained nanocomposites were adoptively transferred to start the treatment. MR imaging clearly visualized the homing of DCVs into lymph nodes. At the end of the treatment, DCVs presented significantly better tumor suppression than DCs or PBS (P < 0.05). Generally, the N-alkyl-PEI2k-LAC/SPIO nanocomposites represent a highly efficient MR imaging platform for siRNA transfection that is potentially useful for in vivo tracking of vaccine cells.

Highlights

Dendritic cells (DCs) have been recruited as a cellular vaccine for tumor immunotherapy but their performance in vivo is generally unsatisfactory [1]
This study aimed to employ this lactosylated analog as a gene delivery platform for carrying IDO small interfering RNA (siRNA) to transfect antitumor DC vaccines (DCVs) and to use it for the treatment of orthotopic 4T1 breast cancer in mouse models while using magnetic resonance (MR) imaging to track the in vivo homing of DCVs to the draining lymph nodes (LNs) (Figure 1)
The dry sample presented as spherical particles in scattering (DLS) and electron microscopy (SEM) images, and SPIO nanocrystals aggregated into nanoclusters in the composites in TEM images (Figure 4)

Summary

Introduction

Dendritic cells (DCs) have been recruited as a cellular vaccine for tumor immunotherapy but their performance in vivo is generally unsatisfactory [1]. Factors such as the weak antigenicity of tumors, failure of vaccine cells to migrate into lymph nodes (LNs) and drive T cell priming, and immune evasion of tumors, etc., are considered the culprits [2]. This study aimed to employ this lactosylated analog as a gene delivery platform for carrying IDO siRNA to transfect antitumor DC vaccines (DCVs) and to use it for the treatment of orthotopic 4T1 breast cancer in mouse models while using MR imaging to track the in vivo homing of DCVs to the draining LNs (Figure 1).

Objectives

Methods

Results

Conclusion