PD-L1 blockade peptide-functionalized NaGdF(4) nanodots for efficient magnetic resonance imaging-guided immunotherapy for breast cancer

PD-L1阻断肽功能化的NaGdF(4)纳米点用于高效的磁共振成像引导乳腺癌免疫治疗

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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 NaGdF(4) nanodots (designated as PDL1-NaGdF(4) 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 NaGdF(4) NDs (designated as Try-NaGdF(4) NDs). MDA-MB-231 tumor could be easily tracked using in vivo MRI with PDL1-NaGdF(4) ND enhancement because the as-prepared PDL1-NaGdF(4) NDs have a high longitudinal relaxivity (r (1)) 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-NaGdF(4) 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-NaGdF(4) NDs were excreted from the body through the kidneys. These results highlight the potential of PDL1-NaGdF(4) NDs as a biocompatible nanomedicine for TNBC diagnosis and immunotherapy.

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