Are caveolae a cellular entry route for non-viral therapeutic delivery systems?

The development of novel therapies increasingly relies on sophisticated delivery systems that allow the drug or gene expression-modifying agent of interest entry into cells. These systems can promote cellular targeting and/or entry, and they vary in size, charge, and functional group chemistry. Their optimization requires an in depth knowledge of the cellular routes of entry in normal and pathological states. Caveolae are plasma membrane invaginations that have the potential to undergo endocytosis. We critically review the literature exploring whether drug or nucleic acid delivery systems exploit and/or promote cellular entry via caveolae. A vast majority of studies employ pharmacological tools, co-localization experiments and very few make use of molecular tools. We provide clarification on how results of such studies should be interpreted and make suggestions for future studies.