Small interfering RNAs (
siRNA) have recently emerged as a new class of
therapeutics with a great potential to revolutionize the treatment of
cancer and other diseases. A specifically designed
siRNA binds and induces post-transcriptional silencing of target genes (
mRNA). Clinical applications of
siRNA-based
therapeutics have been limited by their rapid degradation, poor cellular uptake, and rapid renal clearance following systemic administration. A variety of synthetic and natural nanoparticles composed of
lipids,
polymers, and metals have been developed for
siRNA delivery, with different efficacy and safety profiles. Liposomal nanoparticles have proven effective in delivering
siRNA into
tumor tissues by improving stability and bioavailability. While providing high transfection efficiency and a capacity to form complexes with negatively charged
siRNA, cationic
lipids/
liposomes are highly toxic. Negatively charged
liposomes, on the other hand, are rapidly cleared from circulation. To overcome these problems we developed highly safe and effective neutral
lipid-based nanoliposomes that provide robust gene silencing in
tumors following systemic (
intravenous) administration. This delivery system demonstrated remarkable antitumor efficacy in various orthotopic human
cancer models in animals. Here, we briefly overview this and other
lipid-based approaches with preclinical applications in different
tumor models for
cancer therapy and potential applications as
siRNA-nanotherapeutics in human
cancers.