Stimuli-Responsive Liposomes for Triggered Cargo Release and Activated Cell Delivery

Liposomal nanocarriers are effective for the encapsulation and delivery of a wide range of therapeutic cargo in a manner that improves drug pharmacokinetic properties. However, liposome therapeutic properties could be advanced by enhancing control over cell delivery as well as cargo release. This presentation will describe the development of stimuli-responsive liposomes designed to achieve both of these goals. One approach employs synthetic lipid switches engineered to modulate lipid membrane properties upon contact with disease-associated conditions, such as through programmed chemical reactions and/or conformational changes. In particular, we will focus on encapsulated cargo release triggered by the binding of chemical agents/molecules that are commonly upregulated in diseased cells. A second strategy involves chemically triggering of cell entry. In this design, liposomes are masked as neutral carriers until they encounter stimuli that generate cationic lipids, thereby activating cell entry. The presentation will include the design and synthesis of stimuli-responsive lipid switches, analysis of selectivity of cargo release in the presence of different stimuli, investigation of changes to liposome membrane properties, and evaluation of cellular delivery properties triggered by disease-associated stimuli.