2243P - Immune-modulating magnetic nanoparticles to enhance the immune response for the treatment of breast cancer metastasis and recurrence

Background

The immune-suppressive environment in cancer allows for tumor growth, leading to rapid metastases and recurrences. To effectively treat cancer, it is crucial to reverse this cold tumor environment. CpG, a well-known toll-like receptor 9 agonist, promotes dendritic cells (DCs) maturation and stimulates innate and adaptive immunity. In this study, we combined CpG with functional magnetic nanoparticles (FMNPs) to enhance its delivery to naive DCs, resulting in more efficient activation compared to free CpG delivery.

Methods

The heat-up method used to fabricate FMNPs, which were coated with caffeic acid, polydopamine, and polyethylenimine. The electrostatic force was bind CpG to FMNPs (i.e., CpG-FMNPs), and the degree of binding was estimated using a gel retardation assay. The resulting CpG-FMNPs product analyzed physicochemical properties using electron microscopy, dynamic light scattering, zeta potential, thermogravimetric analysis, and Fourier transform infrared spectroscopy measurements. We confirmed cytotoxicity using the L929 cell line and assessed DCs maturation using flow cytometry.

Results

The fabrication process of the FMNPs involved using various surface chemicals, resulting in changes in physicochemical properties at each step. The final product, CpG-FMNPs, had an average size of approximately 150 nm and contained 8% (weight%) of CpG conjugation. When tested, CpG-FMNPs showed high viability of approximately 90% at a concentration of up to 40 μg/ml and up-regulated 1.5∼2 times of surface markers CD80, CD86, CD40, and MHC-2 on DCs compared to free CpG. When administered intratumorally to the 4T1 orthotopic model, CpG-FMNPs showed a regression in tumor growth.

Conclusions

In this study, we produced FMNPs to efficiently deliver CpG to immature dendritic cells. Our results showed that the same dose of CpG delivered by FMNPs effectively activated DCs. The findings suggest that CpG-FMNPs may be capable of effectively activating DCs in the vicinity of the tumor site. However, further studies are needed to investigate their potential in activating cytotoxic T cells.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

1) National Research Foundation of Korea (2023-00208913) 2) Fourth Stage of Brain Korea 21 Project of the Department of Intelligent Precision Healthcare.

Disclosure

All authors have declared no conflicts of interest.