APTES‑Modified Fe3O4 Nanoparticles Deliver CpG Oligodeoxynucleotides, Enhancing Tumor Immunotherapy and Preventing Metastasis
Abstract
Unmethylated cytosine‑phosphate‑guanine (CpG) oligodeoxynucleotides are potent toll‑like receptor 9 (TLR9) agonists that stimulate a Th1‑biased immune response, offering promise as cancer therapeutics or vaccine adjuvants. Unfortunately, CpG is rapidly degraded by nucleases and shows limited cellular uptake, necessitating high‑dose systemic administration and raising safety concerns. In this study, we engineered a novel delivery platform based on 3‑aminopropyltriethoxysilane (APTES)‑modified Fe3O4 magnetic nanoparticles (FeNPs) that covalently bind CpG through electrostatic interactions. The resulting FeNP/CpG complexes are ~50 nm in diameter, exhibit excellent stability, and enhance CpG internalization by bone‑marrow‑derived dendritic cells (BMDCs). Intratumoral injection of FeNP/CpG in C26 colon‑carcinoma and 4T1 breast‑cancer xenograft models markedly inhibited tumor growth (up to 94.4 % in C26) and reduced spontaneous pulmonary metastases (69 % in 4T1) compared with free CpG or controls. The platform is simple to prepare, biocompatible, and demonstrates a compelling therapeutic index for CpG‑based immunotherapy.
Nanomaterials
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