Multi-functionalized chitosan nanoparticles for enhanced chemotherapy in lung cancer

• Published in: Carbohydrate polymers 2018-09, Vol.195, p.311-320
• Main Authors: Guo, Xueling, Zhuang, Qianfen, Ji, Tianjiao, Zhang, Yinlong, Li, Changjian, Wang, Yueqi, Li, Hong, Jia, Hongying, Liu, Yang, Du, Libo
• Format: Article
• Language: English
• Subjects: Animals; Anticancer; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Aptamer; Cell imaging; Cell Line, Tumor; Chitosan - analogs & derivatives; Drug Carriers - chemistry; Drug delivery; Female; Humans; Lung Neoplasms - drug therapy; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Mice; Mice, Inbred BALB C; Nanoparticle; Nanoparticles - chemistry
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2018.04.087

A multifunctional nanocarrier (MTX@AuNCs-CS-AS1411) was designed and synthesized. The in vivo tumor targeting and anti-cancer efficacy study demonstrated that MTX@AuNCs-CS-AS1411 can improve active tumor-targeting, increase retention and accumulation of MTX in the tumor, resulting in suppress tumor growth. The present study suggested that MTX@AuNCs-CS-AS1411 might have great potential for clinical application. [Display omitted] •A multifunctional nanocarrier (MTX@AuNCs-CS-AS1411) was designed and synthesized.•MTX@AuNCs-CS-AS1411 exhibit high anticancer activity against human lung cancer cells.•MTX@AuNCs-CS-AS1411 could selectively accumulate in exogenous tumor and effectively inhibit tumor growth without overt toxicity. Chemotherapy-based treatment for cancer has made great progress in the past decades. However, there is still a big challenge for the treatment of lung cancer. Herein, a multifunctional nanocarrier was developed through electrostatic interaction between the fluorescent gold nanocluster-conjugated chitosan and the nucleolin targeting AS1411 aptamer. Then methotrexate was loaded into the multifunctional nanocarrier through hydrophobic interaction to obtain the nanodrug carrier systems. The prepared nanodrug carrier systems have an average nanoparticle size of 200 nm with 13.8% drug loading efficiency. The drug release is pH-dependent. The in vitro results demonstrated that the nanodrug carrier systems were selectively taken up by cancer cells in a time-dependent manner and exhibited significantly enhanced anticancer activity in a model of lung cancer A549 cells. The in vivo results showed that intravenous administration of nanodrug carrier systems into BALB/c mice led to accumulation of methotrexate at the tumor site and significantly inhibited the tumor growth but without overt toxicity. The present study suggests that the prepared multifunctional nanocarrier can be used as an effective drug delivery system for anticancer drugs and exhibits great potential in clinical applications.