Tumor targeting based on the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME)

被引:170
作者
Tanaka, T [1 ]
Shiramoto, S [1 ]
Miyashita, M [1 ]
Fujishima, Y [1 ]
Kaneo, Y [1 ]
机构
[1] Fukuyama Univ, Fac Pharm & Pharmaceut Sci, Dept Biopharmaceut, Fukuyama, Hiroshima 7290292, Japan
关键词
drug delivery system; tumor targeting; mitomycin c; macromolecular conjugate; serum albumin; transferrin; enhanced permeability and retention; receptor-mediated endocytosis; intracellular disposition; antitumor activity;
D O I
10.1016/j.ijpharm.2003.09.050
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This review is focused on the macromolecular drug carrier systems by the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME). The effect of EPR is thought to be useful for the targeting of the macromolecular drugs to the tumor tissues on a vasculolymphatic level. The RME reveals the selective recognition, high affinity binding, and immediate internalization for the ligand on a cellular level. In the receptor, recognizing transferrin, a level of expression on the tumor cells is higher than that on the normal cells. We have used serum albumin and transferrin as drug carriers to deliver mitomycin C (MMC) to the tumor tissues and into the tumor cells. The properties of the conjugates of MMC to serum albumin and transferrin were examined in vitro and in vivo. We concluded that MMC could be delivered to the tumor tissue and cells by the use of albumin and transferrin as drug carriers. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:39 / 61
页数:23
相关论文
共 53 条
[1]   INFLUENCE OF CONJUGATION OF DOXORUBICIN TO TRANSFERRIN ON THE IRON UPTAKE BY K562-CELLS VIA RECEPTOR-MEDIATED ENDOCYTOSIS [J].
BERCZI, A ;
RUTHNER, M ;
SZUTS, V ;
FRITZER, M ;
SCHWEINZER, E ;
GOLDENBERG, H .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (01) :427-436
[2]   ADRIAMYCIN CONJUGATES OF HUMAN TRANSFERRIN BIND TRANSFERRIN RECEPTORS AND KILL K562 AND HL-60-CELLS [J].
BERCZI, A ;
BARABAS, K ;
SIZENSKY, JA ;
FAULK, WP .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 300 (01) :356-363
[3]   Differences in the intracellular distribution of acid-sensitive doxorubicin-protein conjugates in comparison to free and liposomal formulated doxorubicin as shown by confocal microscopy [J].
Beyer, U ;
Rothen-Rutishauser, B ;
Unger, C ;
Wunderli-Allenspach, H ;
Kratz, F .
PHARMACEUTICAL RESEARCH, 2001, 18 (01) :29-38
[4]  
CHANG TS, 1978, INT J PEPT PROT RES, V11, P65
[5]  
CIECHANOVER A, 1983, CELL, V32, P267, DOI 10.1016/0092-8674(83)90517-2
[6]  
CIECHANOVER A, 1983, J BIOL CHEM, V258, P9681
[7]   RECEPTOR-MEDIATED ENDOCYTOSIS - THE INTRACELLULAR JOURNEY OF TRANSFERRIN AND ITS RECEPTOR [J].
DAUTRYVARSAT, A .
BIOCHIMIE, 1986, 68 (03) :375-381
[8]   THE BIOLOGY OF TRANSFERRIN [J].
DEJONG, G ;
VANDIJK, JP ;
VANEIJK, HG .
CLINICA CHIMICA ACTA, 1990, 190 (1-2) :1-46
[9]   SYNTHESIS AND EVALUATION OF MACROMOLECULAR PRODRUGS OF MITOMYCIN-C [J].
DEMARRE, A ;
SOYEZ, H ;
SCHACHT, E ;
SHOAIBI, MA ;
SEYMOUR, LW ;
RIHOVA, B .
JOURNAL OF CONTROLLED RELEASE, 1995, 36 (1-2) :87-97
[10]   THE UP-AND-DOWN METHOD FOR SMALL SAMPLES [J].
DIXON, WJ .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1965, 60 (312) :967-978