A tumor-targeted nanodelivery system to improve early MRI detection of cancer

被引:48
作者
Pirollo, Kathleen F.
Dagata, John
Wang, Paul
Freedman, Matthew
Vladar, Andras
Fricke, Stanley
Ileva, Lilia
Zhou, Qi
Chang, Esther H.
机构
[1] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA
[2] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA
[3] Howard Univ, Washington, DC 20059 USA
来源
MOLECULAR IMAGING | 2006年 / 5卷 / 01期
关键词
nanocomplex; tumor targeting; Magnevist (R); MRI; early detection;
D O I
10.2310/7290.2006.00005
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The development of improvements in magnetic resonance imaging (MRI) that would enhance sensitivity, leading to earlier detection of cancer and visualization of metastatic disease, is an area of intense exploration. We have devised a tumor-targeting, liposomal nanodelivery platform for use in gene medicine. This systemically administered nanocomplex has been shown to specifically and efficiently deliver both genes and oligonucleotides to primary and metastatic tumor cells, resulting in significant tumor growth inhibition and even tumor regression. Here we examine the effect on MRI of incorporating conventional MRI contrast agent Magnevist(R) into our anti-transferrin receptor single-chain antibody (TfRscFv) liposomal complex. Both in vitro and in an in vivo orthotopic mouse model of pancreatic cancer; we show increased resolution and image intensity with the complexed Magnevist(R). Using advanced microscopy techniques (scanning electron microscopy and scanning probe microscopy), we also established that the Magnevist(R) is in fact encapsulated by the liposome in the complex and that the complex still retains its nanodimensional size. These results demonstrate that this TfRscFv-liposome-Magnevist(R) nanocomplex has the potential to become a useful tool in early cancer detection.
引用
收藏
页码:41 / 52
页数:12
相关论文
共 33 条
[1]  
ALISAUSKUS R, 1995, CANCER RES, V55, pS5743
[2]   SINGLE-CHAIN IMMUNOTOXINS DIRECTED AT THE HUMAN TRANSFERRIN RECEPTOR CONTAINING PSEUDOMONAS EXOTOXIN-A OR DIPHTHERIA-TOXIN - ANTI-TFR(FV)-PE40 AND DT388-ANTI-TFR(FV) [J].
BATRA, JK ;
FITZGERALD, DJ ;
CHAUDHARY, VK ;
PASTAN, I .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (04) :2200-2205
[3]   Receptor ligand-facilitated gene transfer: Enhancement of liposome-mediated gene transfer and expression by transferrin [J].
Cheng, PW .
HUMAN GENE THERAPY, 1996, 7 (03) :275-282
[4]   Characterization of a targeted gene carrier, lactose-polyethylene glycol-grafted poly-L-lysine, and its complex with plasmid DNA [J].
Choi, YH ;
Liu, F ;
Choi, JS ;
Kim, SW ;
Park, JS .
HUMAN GENE THERAPY, 1999, 10 (16) :2657-2665
[5]  
Cristiano RJ, 1996, CANCER GENE THER, V3, P49
[6]  
Degani H, 2003, THROMB HAEMOSTASIS, V89, P25
[7]   Magnetite defines a vertebrate magnetoreceptor [J].
Diebel, CE ;
Proksch, R ;
Green, CR ;
Neilson, P ;
Walker, MM .
NATURE, 2000, 406 (6793) :299-302
[8]   Nanoscopic structure of DNA condensed for gene delivery [J].
Dunlap, DD ;
Maggi, A ;
Soria, MR ;
Monaco, L .
NUCLEIC ACIDS RESEARCH, 1997, 25 (15) :3095-3101
[9]   BREAST-CARCINOMA AND THE ROLE OF IRON-METABOLISM - A CYTOCHEMICAL, TISSUE-CULTURE, AND ULTRASTRUCTURAL-STUDY [J].
ELLIOTT, RL ;
ELLIOTT, MC ;
WANG, F ;
HEAD, JF .
BREAST CANCER: FROM BIOLOGY TO THERAPY, 1993, 698 :159-166
[10]   Contact deformation of liposome in the presence of osmosis [J].
Foo, JJ ;
Chan, V ;
Liu, KK .
ANNALS OF BIOMEDICAL ENGINEERING, 2003, 31 (10) :1279-1286