Best Group’s Recent Work
Recent work in the Best Group has culminated in the development of stimuli-responsive liposomes for drug delivery designed to release therapeutic cargo when they come into contact with diseased cells, specifically based on overexpressed enzymes and reactive oxygen species. “These smart liposomes show strong prospects for advancing drug delivery by targeting therapeutics directly to the site of the disease,” Jinchao Lou, graduate student in the Best Group, said.
Liposomes are effective nanocarriers for drug delivery due to their ability to encapsulate and deliver a wide variety of therapeutic cargo to cells. Nevertheless, liposome delivery would be improved by enhancing the ability to control the release of contents within diseased cells. Toward this end, stimuli-responsive liposomes, in which the drug carrier decomposes when it comes in contact with conditions associated with disease, are of great interest for enhancing drug potency while minimizing side effects.
While various stimuli have been explored for triggering liposome release, both enzymes and reactive oxygen species (ROS) provide excellent targets due to their key roles in biology and overabundance in diseased cells. In two separate papers, the Best Group presented a general approach to enzyme‐responsive liposomes exploiting targets that are commonly aberrant in disease, including esterases, phosphatases, and β‐galactosidases (Chem. Eur. J. 2020, 26, 8597-8607), as well as an ROS-responsive liposomal delivery platform (Bioconjugate Chem. 2020, 31, 2220-2230).
In both of the cases, responsive lipids designed to target each stimulus were designed and synthesized bearing a responsive headgroup attached via a self‐immolating linker to a non‐bilayer lipid scaffold. In this way, stimulus addition triggers chemical lipid decomposition in a manner that disrupts membrane integrity and releases contents. Release properties were fully characterized by fluorescence-based dye leakage assays, dynamic light scattering and electron microscopy, among other techniques.
Due to their recent works in this field, the Best group was also invited to write a review describing advances in the design of stimuli-responsive liposome strategies for drug delivery with an eye towards emerging trends in the field (Chem. Phys. Lipids. In Press. DOI 10.1016/j.chemphyslip.2020.104966). Smart liposomes show strong prospects for advancing drug delivery by targeting drugs directly to the site of the disease.