PD-L1 blockade peptide-functionalized NaGdF4 nanodots for efficient magnetic resonance imaging-guided immunotherapy for breast cancer

Abstract

Immune checkpoint blockade (ICB) inhibitors have shown great promise for the treatment of numerous types of cancers, including triple-negative breast cancer (TNBC), by interrupting immunosuppressive checkpoints. Herein, programmed cell death ligand 1 (PD-L1) blockade peptide-functionalized NaGdF₄ nanodots (designated as PDL1-NaGdF₄ NDs) were prepared for magnetic resonance imaging (MRI)-guided TNBC immunotherapy through covalent conjugation of the PD-L1 blockade peptide (sequence, CALNNCVRARTR) with tryptone-capped NaGdF₄ NDs (designated as Try-NaGdF₄ NDs). MDA-MB-231 tumor could be easily tracked using in vivo MRI with PDL1-NaGdF₄ ND enhancement because the as-prepared PDL1-NaGdF₄ NDs have a high longitudinal relaxivity (r₁) value (22.8 mM⁻¹ S⁻¹) and accumulate in the tumor site through binding with programmed cell death ligand-1 (PD-L1)-overexpressed cells. A series of in vitro/in vivo results demonstrated that the PDL1-NaGdF₄ NDs could effectively suppress MDA-MB-231 tumor growth in mice (66% volume ratio) by inhibiting migration and proliferation of tumor cells. In addition, the results of pharmacokinetic study showed that the PDL1-NaGdF₄ NDs were excreted from the body through the kidneys. These results highlight the potential of PDL1-NaGdF₄ NDs as a biocompatible nanomedicine for TNBC diagnosis and immunotherapy.