Legumain-responsive functional gold nanoparticles for drug targeting delivery and treatment of subcutaneous xenograft tumor
10.16438/j.0513-4870.2017-0847
- VernacularTitle:豆荚蛋白酶响应的功能化金纳米粒用于皮下移植瘤靶向药物递送和治疗
- Author:
Shao-bo RUAN
1
;
Qin HE
1
;
Hui-le GAO
1
Author Information
1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West School of Pharmacy, Sichuan University, Chengdu 610041, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
legumain;
metal nanoparticle;
click chemistry;
aggregation;
retention
- From:
Acta Pharmaceutica Sinica
2017;52(11):1756-1762
- CountryChina
- Language:Chinese
-
Abstract:
Legumain, a kind of asparaginyl endopeptidase, is overexpressed in highly metastatic and highly aggressive tumor, which can undergo an enzymatic hydrolysis of substrates. We proposed a legumain-responsive functional gold nanoparticle (GNP) drug delivery system (GNPs-A&C), which was consist of Ala-Ala-Asn-Cys-Lys (AK) modified GNPs (GNPs-AK) and 2-cyano-6-aminobenzothiazole (CABT) modified GNPs (GNPs-CABT). In the circulation system, the GNPs-A&C could passively target to the tumor site through the enhanced permeability and retention (EPR) effect. Then the overexpressed legumain specifically cleave the peptide to exposure the 1,2-thiolamino group, which could take place click reaction with the cyano group of CABT, leading to the aggregation of two GNPs, these aggregates of GNPs with increased size were more likely to retain within tumor site. In vivo fluorescent imaging demonstrated GNPs-A&C could acquire an enhanced accumulation in legumain-overexpressed C6 tumor. Importantly, after tethering DOX, the GNPs-DOX-A&C showed an excellent anti-tumor effect with reduced cardiotoxicity.
