Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress

被引:119
作者
Muro, S
Cui, XM
Gajewski, C
Murciano, JC
Muzykantov, VR
Koval, M
机构
[1] Univ Penn, Sch Med, Inst Environm Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2003年 / 285卷 / 05期
关键词
drug delivery; endocytosis; microtubules; lysosomes;
D O I
10.1152/ajpcell.00099.2003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nanotechnologies promise new means for drug delivery. ICAM-1 is a good target for vascular immunotargeting of nanoparticles to the perturbed endothelium, although endothelial cells do not internalize monomeric anti-ICAM-1 antibodies. However, coupling ICAM-1 antibodies to nanoparticles creates multivalent ligands that enter cells via an amiloride-sensitive endocytic pathway that does not require clathrin or caveolin. Fluorescence microscopy revealed that internalized anti-ICAM nanoparticles are retained in a stable form in early endosomes for an unusually long time (1-2 h) and subsequently were degraded following slow transport to lysosomes. Inhibition of lysosome acidification by chloroquine delayed degradation without affecting anti-ICAM trafficking. Also, the microtubule disrupting agent nocodazole delayed degradation by inhibiting anti-ICAM nanoparticle trafficking to lysosomes. Addition of catalase to create anti-ICAM nanoparticles with antioxidant activity did not affect the mechanisms of nanoparticle uptake or trafficking. Intracellular anti-ICAM/catalase nanoparticles were active, because endothelial cells were resistant to H2O2-induced oxidative injury for 1-2 h after nanoparticle uptake. Chloroquine and nocodazole increased the duration of antioxidant protection by decreasing the extent of anti-ICAM/catalase degradation. Therefore, the unique trafficking pathway followed by internalized anti-ICAM nanoparticles seems well suited for targeted delivery of therapeutic enzymes to endothelial cells and may provide a basis for treatment of acute vascular oxidative stress.
引用
收藏
页码:C1339 / C1347
页数:9
相关论文
共 55 条
[1]  
[Anonymous], ENDOCYTOSIS
[2]   Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against oxidative stress [J].
Atochina, EN ;
Balyasnikova, IV ;
Danilov, SM ;
Granger, DN ;
Fisher, AB ;
Muzykantov, VR .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1998, 275 (04) :L806-L817
[3]   Ligand coated nanosphere adhesion to E- and P-selectin under static and flow conditions [J].
Blackwell, JE ;
Dagia, NM ;
Dickerson, JB ;
Berg, EL ;
Goetz, DJ .
ANNALS OF BIOMEDICAL ENGINEERING, 2001, 29 (06) :523-533
[4]   ADHESION MOLECULES - A NEW TARGET FOR IMMUNOLIPOSOME-MEDIATED DRUG-DELIVERY [J].
BLOEMEN, PGM ;
HENRICKS, PAJ ;
VANBLOOIS, L ;
VANDENTWEEL, MC ;
BLOEM, AC ;
NIJKAMP, FP ;
CROMMELIN, DJA ;
STORM, G .
FEBS LETTERS, 1995, 357 (02) :140-144
[5]   Nanoparticles in cancer therapy and diagnosis [J].
Brigger, I ;
Dubernet, C ;
Couvreur, P .
ADVANCED DRUG DELIVERY REVIEWS, 2002, 54 (05) :631-651
[6]   Inhibition of eosinophil rolling and recruitment in P-selectin- and intracellular adhesion molecule-1-deficient mice [J].
Broide, DH ;
Humber, D ;
Sriramarao, P .
BLOOD, 1998, 91 (08) :2847-2856
[7]   Using nuclear targeting signals to enhance non-viral gene transfer [J].
Chan, CK ;
Jans, DA .
IMMUNOLOGY AND CELL BIOLOGY, 2002, 80 (02) :119-130
[8]   Study of the drug release mechanism from tyrphostin AG-1295-loaded nanospheres by in situ and external sink methods [J].
Chorny, M ;
Fishbein, I ;
Danenberg, HD ;
Golomb, G .
JOURNAL OF CONTROLLED RELEASE, 2002, 83 (03) :401-414
[9]   Immunotargeting of glucose oxidase to endothelium in vivo causes oxidative vascular injury in the lungs [J].
Christofidou-Solomidou, M ;
Pietra, GG ;
Solomides, CC ;
Arguiris, E ;
Harshaw, D ;
Fitzgerald, GA ;
Albelda, SM ;
Muzykantov, VR .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 278 (04) :L794-L805
[10]   Attenuation of rat lung isograft reperfusion injury with a combination of anti-ICAM-1 and anti-beta 2 integrin monoclonal antibodies [J].
DeMeester, SR ;
Molinari, MA ;
Shiraishi, T ;
Okabayashi, K ;
Manchester, JK ;
Wick, MR ;
Cooper, JD ;
Patterson, GA .
TRANSPLANTATION, 1996, 62 (10) :1477-1485