In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy

被引:39
作者
Ak, Guliz [1 ]
Yilmaz, Habibe [1 ]
Gunes, Aybike [1 ]
Sanlier, Senay Hamarat [1 ]
机构
[1] Ege Univ, Fac Sci, Dept Biochem, Izmir, Turkey
关键词
Ovarian cancer; targeted drug delivery; folate receptor; magnetic nanoparticles; doxorubicin; erythrocyte vesicle; COATED MAGNETITE; NANOPARTICLES; DOXORUBICIN; FUNCTIONALIZATION; BIODISTRIBUTION; NANOCARRIERS; RESISTANCE; STABILITY; MICELLES; DESIGN;
D O I
10.1080/21691401.2018.1439838
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Doxorubicin is widely used anticancer drug; however, use of doxorubicin is limited. Under externally applied magnetic field, magnetic agents can help to transport drug directly to tumor. Folate receptor is overexpressed in ovarian carcinomas. In this study, we aimed to develop magnetically responsive and folate receptor-targeted biomimetic drug delivery system for ovarian cancer therapy. Doxorubicin-loaded and glucose/gluconic acid-coated magnetic nanoparticles were synthesized and erythrocyte membrane vesicles were used for coating of nanoparticles. Folate ligand was anchored to surface so as to target receptor. Hydrodynamic size of nanocarrier was found as 91.2 +/- 20.8nm. The results showed that delivery system has controlled drug release profile and biocompatible features. In folate-free medium, folate receptor-targeted nanocarrier showed 10.33-fold lower IC50 values for A2780 cells and 3.93-fold lower for OVCAR3 cells compared to non-targeted nanoparticles and demonstrated more cytotoxicity against ovarian cancer cells. Moreover, magnetically and folate receptor-targeted doxorubicin delivery system was significantly more effective for therapy of xenografted nude mice than free doxorubicin based on tumor shrinkages and biochemical parameters. In conclusion, it can be suggested that folate ligand-attached and biomimetically designed magnetic drug delivery system have advantages and potential for targeted ovarian cancer therapy.
引用
收藏
页码:S926 / S937
页数:12
相关论文
共 49 条
[1]   Preparation of magnetically responsive albumin nanospheres and in vitro drug release studies [J].
Ak, Guliz ;
Yilmaz, Habibe ;
Sanlier, Senay Hamarat .
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY, 2014, 42 (01) :18-26
[2]   SYNTHESIS OF FOLATE RECEPTOR-TARGETED AND DOXORUBICIN-COUPLED CHEMOTHERAPEUTIC NANOCONJUGATE AND RESEARCH INTO ITS MEDICAL APPLICATIONS [J].
Ak, Guliz ;
Sanlier, Senay Hamarat .
PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, 2012, 42 (06) :551-563
[3]   HPLC quantification of doxorubicin in plasma and tissues of rats treated with doxorubicin loaded poly(alkylcyanoacrylate) nanoparticles [J].
Alhareth, Khairallah ;
Vauthier, Christine ;
Gueutin, Claire ;
Ponchel, Gilles ;
Moussa, Fathi .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2012, 887 :128-132
[4]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[5]   Folic acid conjugated nanoliposomes as promising carriers for targeted delivery of bleomycin [J].
Chiani, Mohsen ;
Norouzian, Dariush ;
Shokrgozar, Mohammad Ali ;
Azadmanesh, Kayhan ;
Najmafshar, Aazam ;
Mehrabi, Mohammad Reza ;
Akbarzadeh, Azim .
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY, 2018, 46 (04) :757-763
[6]   Therapeutic nanoparticles for drug delivery in cancer [J].
Cho, Kwangjae ;
Wang, Xu ;
Nie, Shuming ;
Chen, Zhuo ;
Shin, Dong M. .
CLINICAL CANCER RESEARCH, 2008, 14 (05) :1310-1316
[7]   Magnetic nanoparticles and targeted drug delivering [J].
Chomoucka, Jana ;
Drbohlavova, Jana ;
Huska, Dalibor ;
Adam, Vojtech ;
Kizek, Rene ;
Hubalek, Jaromir .
PHARMACOLOGICAL RESEARCH, 2010, 62 (02) :144-149
[8]   Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting [J].
Cole, Adam J. ;
David, Allan E. ;
Wang, Jianxin ;
Galban, Craig J. ;
Hill, Hannah L. ;
Yang, Victor C. .
BIOMATERIALS, 2011, 32 (08) :2183-2193
[9]  
Corona G, 1998, INT J CANCER, V75, P125, DOI 10.1002/(SICI)1097-0215(19980105)75:1<125::AID-IJC19>3.0.CO
[10]  
2-F