Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.
Siyao WangWangbo JiaoBin YanXiaofei LiuQianqian TangYihan ZhangChen LiangXun WangYi LyuHai Ming FanXiaoli LiuPublished in: Nano letters (2024)
Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.
Keyphrases
- molecularly imprinted
- cancer therapy
- cell death
- immune response
- nk cells
- signaling pathway
- poor prognosis
- drug delivery
- binding protein
- dna damage
- transcription factor
- cell cycle
- mass spectrometry
- risk assessment
- gene expression
- inflammatory response
- cell proliferation
- radiation therapy
- iron oxide
- single cell
- amino acid
- protein protein
- oxidative stress
- long non coding rna
- toll like receptor
- dna methylation
- squamous cell carcinoma
- high resolution
- reactive oxygen species