Delivery of lipoplexes for genotherapy of solid tumours: Role of vascular endothelial cells

被引:24
作者
Dass, CR
Su, T
机构
[1] Johnson & Johnson Res, Strawberry Hills 2012, Australia
[2] Univ New S Wales, Fac Med, Dept Immunol, Kensington, NSW 2217, Australia
关键词
D O I
10.1211/0022357001777450
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The cells constituting a solid tumour may vary considerably due to biological disparities, but for a solid tumour to pose as a threat to its host, an adequate blood supply has to be established. Although neovascularisation may have dire consequences for the host, it provides a common route by which tumours in general may be reached and eradicated by drugs. The fact that a tumour's vasculature is relatively more permeable than healthy host tissue means that selective delivery of drugs may be achieved. A closer examination of the role played by the cells making up the tumour vascular bed, vascular endothelial cells (VECs), is required to facilitate design of ways for enhancing drug delivery to solid tumours via the vascular route. VECs have two major roles in the body, barrier and transport, both of which are highly pertinent to drug delivery. This review discusses the factors regulating VEC function, and how these cells may be manipulated in-vivo to improve the selective delivery of lipoplexes, carriers for gene therapy constructs, to solid tumours. It also discusses how genotherapeutic drugs may be targeted against tumour VECs on the premise that by killing these cells, the tumour itself will perish.
引用
收藏
页码:1301 / 1317
页数:17
相关论文
共 200 条
[1]   GROWTH-REGULATION OF THE VASCULAR SYSTEM - EVIDENCE FOR A METABOLIC HYPOTHESIS [J].
ADAIR, TH ;
GAY, WJ ;
MONTANI, JP .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (03) :R393-R404
[2]   PERMEABILITY CHARACTERISTICS OF CULTURED ENDOTHELIAL-CELL MONOLAYERS [J].
ALBELDA, SM ;
SAMPSON, PM ;
HASELTON, FR ;
MCNIFF, JM ;
MUELLER, SN ;
WILLIAMS, SK ;
FISHMAN, AP ;
LEVINE, EM .
JOURNAL OF APPLIED PHYSIOLOGY, 1988, 64 (01) :308-322
[3]   TUMOR VASCULATURE - A POTENTIAL THERAPEUTIC TARGET [J].
BAILLIE, CT ;
WINSLET, MC ;
BRADLEY, NJ .
BRITISH JOURNAL OF CANCER, 1995, 72 (02) :257-267
[4]   Cationic lipids are essential for gene delivery mediated by intravenous administration of lipoplexes [J].
Barron, LG ;
Uyechi, LS ;
Szoka, FC .
GENE THERAPY, 1999, 6 (06) :1179-1183
[5]   Lipoplex-mediated gene delivery to the lung occurs within 60 minutes of intravenous administration [J].
Barron, LG ;
Gagné, L ;
Szoka, FC .
HUMAN GENE THERAPY, 1999, 10 (10) :1683-1694
[6]   Evidence for three-dimensional interlayer correlations in cationic lipid-DNA complexes as observed by cryo-electron microscopy [J].
Battersby, BJ ;
Grimm, R ;
Huebner, S ;
Cevc, G .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1998, 1372 (02) :379-383
[7]   The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor-associated antigen to induce immune responses and protective immunity in mice [J].
Bei, R ;
Guptill, V ;
Masuelli, L ;
Kashmiri, SVS ;
Muraro, R ;
Frati, L ;
Schlom, J ;
Kantor, J .
JOURNAL OF IMMUNOTHERAPY, 1998, 21 (03) :159-169
[8]  
Boucher Y, 1996, CANCER RES, V56, P4264
[9]  
BOUCHER Y, 1995, AM ASS CANC RES M TO
[10]   BRAIN MICROVESSEL ENDOTHELIAL-CELLS IN TISSUE-CULTURE - A MODEL FOR STUDY OF BLOOD-BRAIN-BARRIER PERMEABILITY [J].
BOWMAN, PD ;
ENNIS, SR ;
RAREY, KE ;
BETZ, AL ;
GOLDSTEIN, GW .
ANNALS OF NEUROLOGY, 1983, 14 (04) :396-402