Delivery of lipoplexes for genotherapy of solid tumours: role of vascular endothelial cells.
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.
Dass
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Johnson & Johnson Research, Strawberry Hills, Australia. cdass@medau.jnj.com
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D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D015316:Genetic Therapy; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic; D010539:Permeability
D004337:Drug Carriers; D008055:Lipids