PDF(Pubmed)
Abstract：
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-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 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 NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r1) value (21.87 mM-1S-1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 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-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.
摘要：
C-X-C基序趋化因子受体4（CXCR4）是乳腺癌的有希望的治疗靶标，因为它在包括三阴性乳腺癌（TNBC）在内的所有乳腺癌分子亚型的细胞表面上过表达。在这里，CXCR4拮抗肽-NaGdF4纳米点缀合物（称为抗CXCR4-NaGdF4NDs）已通过将C-X-C基序趋化因子12（CXCL12）衍生的环肽与胰蛋白胨包被的NaGdF4纳米点（直径5±0.5nm，称为Try-NaGdF4ND)。制备的抗CXCR4-NaGdF4ND表现出高纵向弛豫率（r1）值（21.87mM-1S-1），合理的生物相容性和良好的肿瘤积累能力。抗CXCR4-NaGdF4NDs的特征提高了肿瘤MRI敏感性，并促进了体内小鼠携带MDA-MB-231肿瘤模型注射后的肿瘤生物治疗。使用抗CXCR4-NaGdF4ND的MRI引导的生物治疗能够抑制46%的肿瘤生长。此外,在注射后24小时,在小鼠尿液中发现约47%注射剂量的抗CXCR4-NaGdF4ND。这些发现表明，抗CXCR4-NaGdF4NDs可以用作肾脏可清除的纳米药物，用于乳腺癌的生物治疗和MRI。
