The challenge of liposomes in gene therapy

Recently , l iposomes have gained a special interest as gene delivery systems: over 30 human clinical trials for gene del ivery using cationic l iposomes have been approved; al l these del ivery methods use intratumoral, subcutaneous and other local delivery but not systemic delivery due to the toxicity of cat ionic l ipids . Stealth l iposomes (coated with polyethyleneglycol to camouflage the l iposome and evade detect ion by the immune system) have a remarkable longevity in body fluids, have negligible toxicity with respect to their l ipid components, reduce the toxicity of the encapsulated drug, and can deliver efficiently their doxorubicin payload (DOXIL) or cis-platin to tumor les ions . The mechanism of stealth l iposome accumulation in tumors involves their extravasation through gaps in the endothelium of tumor vessels. DOXIL can sustain a much higher concentration of Doxorubicin in tumor tissue compared to free drug administration at comparable doses. Liposomes tagged with folate-PEG or with antibodies can target specific t issues . We propose that “stealth” l iposomes, could f ind future applications to systemically deliver plasmid DNA with therapeutic genes (p53 , H S V tk , angiostatin) to primary tumors and their metastases leading to complete cancer eradication.