Abstract:
Invasion and metastasis are the leading causes of death of patients with CRC. 5-Fluorouracil is widely used in clinic practice as the basic chemotherapy drug for CRC. However, it is inefficient in inhibiting tumor metastasis. MicroRNA-10b is uninvolved in regulating the growth of primary tumors; however, it could induce early tumor metastases and is a key regulator of chemotherapeutic resistance to 5-FU. A multifunctional nanovehicle that can carry small molecule drugs not only through the hydrophobic pockets of conjugated β-cyclodextrin but also through electrostatic interaction between the conjugated peptides and siRNA to target functional genes is previously developed. In this study, a nanovehicle, named GCD, with epithelium growth factor receptor (EGFR)-targeted characteristics to simultaneously deliver chemotherapeutic and nucleotide drugs to distinct targets in CRC, is employed. These data show that co-delivery of 5-FU and anti-miR-10b can be effectively applied to targeted therapy of EGFR-overexpressed CRC, particularly inhibiting the metastasis of CRC. Furthermore, the therapeutic effect of this combination on tumor xenograft models derived from patients with CRC is evaluated. Taken together, this study may provide insights into the inhibition of tumor growth and metastasis simultaneously.
摘要:
结直肠癌(CRC)的侵袭和转移是导致CRC患者死亡的主要原因。5-氟尿嘧啶(5-FU)作为结直肠癌的基础化疗药物已广泛应用于临床。然而,抑制肿瘤转移是无效的。microRNA-10b(miR-10b)不参与调节原发性肿瘤的生长;然而,它可以诱导早期肿瘤转移,是5-FU化疗耐药的关键调节因子。我们以前开发了一种多功能纳米载体,它不仅可以通过缀合的β-环糊精(β-CD)的疏水性口袋携带小分子药物,还可以通过缀合的肽和货物siRNA之间的静电相互作用来靶向功能基因。在这项研究中,我们使用了一种纳米载体,名为GCD,具有EGFR靶向特征,可同时将化疗(5-FU)和核苷酸(miR-10b抑制剂)药物递送至CRC的不同靶标。我们的数据显示,5-FU和抗miR-10b的共同递送可以有效地应用于靶向EGFR过表达的CRC,特别是在体外和体内抑制CRC的转移。此外,我们评估了该组合对源自CRC患者的肿瘤异种移植模型的治疗效果.一起来看,这项研究可能为同时抑制肿瘤生长和转移提供见解。本文受版权保护。保留所有权利。