Employing antagonistic C-X-C motif chemokine receptor 4 antagonistic peptide functionalized NaGdF nanodots for magnetic resonance imaging-guided biotherapy of breast cancer.

C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF nanodot conjugates (termed as anti-CXCR4-NaGdF NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF NDs). The as-prepared anti-CXCR4-NaGdF NDs exhibits high longitudinal relaxivity (r) value (21.87 mMS), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.