Shi Leilei, Hu Yi, Lin Ang, Ma Chuan, Zhang Chuan, Su Yue, Zhou Linzhu, Niu Yumei, Zhu Xinyuan
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
Department of Medicine, Immunology and Allergy Unit, Karolinska Institute , Stockholm, SE 17176, Sweden.
Bioconjug Chem. 2016 Dec 21;27(12):2943-2953. doi: 10.1021/acs.bioconjchem.6b00643. Epub 2016 Dec 8.
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide, especially in developed countries. Although patients' overall survival has been improved by either conventional chemotherapy or newly developed anti-angiogenesis treatment based on its highly vascularized feature, the relatively low therapeutic efficacy and severe side effects remain big problems in clinical practice. In this study, we describe an easy method to construct a novel matrix metalloproteinase-2 (MMP-2) responsive nanocarrier, which can load hydrophobic agents (camptothecin and sorafenib) with high efficiency to exert synergistic efficacy for CRC treatment. The drug-containing nanoparticles can particularly respond to the MMP-2 and realize the controlled release of payloads at the tumor site. Moreover, both in vitro and in vivo studies have demonstrated that this responsive nanoparticle exhibits much higher therapeutic efficacy than that of single antitumor agents or combined drugs coadministrated in traditional ways.
结直肠癌（CRC）是全球最常被诊断出的癌症之一，在发达国家尤为如此。尽管基于其高度血管化的特征，传统化疗或新开发的抗血管生成治疗已改善了患者的总生存期，但相对较低的治疗效果和严重的副作用在临床实践中仍然是大问题。在本研究中，我们描述了一种构建新型基质金属蛋白酶-2（MMP-2）响应性纳米载体的简便方法，该纳米载体可以高效负载疏水性药物（喜树碱和索拉非尼），从而对CRC治疗发挥协同疗效。含药纳米颗粒能够特别响应MMP-2，并在肿瘤部位实现有效载荷的控释。此外，体外和体内研究均表明，这种响应性纳米颗粒比单一抗肿瘤药物或以传统方式联合给药的联合药物具有更高的治疗效果。
