The challenge of liposomes in gene therapy

摘要

Recently, liposomes have gained a special interest as gene delivery systems: over 30 human clinical trials for gene delivery using cationic liposomes have been approved; all these delivery methods use intratumoral, subcutaneous and other local delivery but not systemic delivery due to the toxicity of cationic lipids. Stealth liposomes (coated with polyethyleneglycol to camouflage the liposome and evade detection by the immune system) have a remarkable longevity in body fluids, have negligible toxicity with respect to their lipid components, reduce the toxicity of the encapsulated drug, and can deliver efficiently their doxorubicin payload (DOXIL) or cis-platin to tumor lesions. The mechanism of stealth liposome 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 tissues. We propose that “stealth” liposomes, could find future applications to systemically deliver plasmid DNA with therapeutic genes (p53, HSV-tk, angiostatin) to primary tumors and their metastases leading to complete cancer eradication.