Targeted delivery of doxorubicin by CSA-binding nanoparticles for choriocarcinoma treatment

Drug Delivery

Lintao Cai¹  Mingbin Zheng¹  Shoujun Li²  Jinyu Han³  Guogang Cheng³  Jie Chen³  Baobei Wang³  Baozhen Zhang³  Tianxia Xiao³  Xiujun Fan³  Mengxia Li³  Jian Zhang³ 

[1] Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China;Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, China;College of Veterinary Medicine, South China Agricultural University, Guangzhou, Chin;Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China;

关键词: Chondroitin sulfate A;    CSA-bind peptide;    nanoparticles;    drug delivery;    tumor targeting;    choriocarcinoma;   

DOI  :  10.1080/10717544.2018.1435750

来源: publisher

【 摘 要 】

Gestational trophoblastic neoplasia (GTN) can result from the over-proliferation of trophoblasts. Treatment of choriocarcinoma, the most aggressive GTN, currently requires high doses of systemic chemotherapeutic agents, which result in indiscriminate drug distribution and severe toxicity. To overcome these disadvantages and enhance the chemotherapeutic efficacy, chondroitin sulfate A (CSA)-binding nanoparticles were developed for the targeted delivery of doxorubicin (DOX) to choriocarcinoma cells using a synthetic CSA-binding peptide (CSA-BP), derived from malarial protein, which specifically binds to the CSA exclusively expressed in the placental trophoblast. CSA-BP-conjugated nanoparticles rapidly bonded to choriocarcinoma (JEG3) cells and were efficiently internalized into the lysosomes. Moreover, CSA-BP modification significantly increased the anti-cancer activity of the DOX-loaded nanoparticles in vitro. Intravenous injections of CSA-BP-conjugated nanoparticles loaded with indocyanine green (CSA-INPs) were rapidly localized to the tumor. The CSA-targeted nanoparticles loaded with DOX (CSA-DNPs) strongly inhibited primary tumor growth and, more importantly, significantly suppressed metastasis in vivo. Collectively, our results highlight the potential of the CSA-BP-decorated nanoparticles as an alternative targeted delivery system of chemotherapeutic agents for treating choriocarcinoma and for developing new GTN therapies based on drug targeting.

【 授权许可】

CC BY