Particle-mediated intravascular delivery of oligonucleotides to tumors: associated biology and lessons from genotherapy.
For a solid tumor to become life-threatening, an adequate blood supply has to be established. Although neovascularization has dire consequences for the host, it furnishes a common route through which tumors may be accessed and eradicated by drugs. The fact that a tumor's vasculature is relatively more permeable than that of healthy host tissue means selective delivery of drugs may be achieved. The role played by the cells making up the tumor vascular bed, vascular endothelial cells (VECs), has to be evaluated closely in attempts to design ways for enhancing drug delivery to solid tumors via the vasculature. The two major roles of VECs in the body, as barrier and as transport, are both highly pertinent to drug delivery. Our review examines how VECs may be manipulated in vivo to improve the selective delivery of carriers for oligonucleotide constructs to solid tumors. It also discusses how oligonucleotide drugs may be targeted against tumor VECs on the premise that by killing these cells, the tumor itself will perish. Cationic liposomes and microspheres are the major delivery vehicles discussed, with added analyses of such other nucleic acid carriers as nanospheres, dendrimers, and polyethyleneimine.
Dass
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Johnson & Johnson Research, Strawberry Hills, Australia. cdass@medau.jnj.com
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D000818:Animals; D001692:Biological Transport; D002199:Capillary Permeability; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008081:Liposomes; D008863:Microspheres; D009369:Neoplasms / Q000098:blood supply* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000628:therapy; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics
D004337:Drug Carriers; D008081:Liposomes; D009841:Oligonucleotides