(38c) ROS-Induced Disruption of Vesicles: A Potential Strategy to Enhance Cancer Radiotherapy

Catanionic vesicles are nanocontainers (size ~ 100 nm) that are formed by the self-assembly of two oppositely charged single-tail surfactants. They have an aqueous interior surrounded by a bilayer membrane formed by these surfactants. Solutes encapsulated in these vesicles slowly get released through the bilayer via diffusion. However, high solute concentrations usually cannot be achieved using passive diffusion from vesicle membranes. Hence, researchers have been working towards creating stimuli-responsive vesicles for enabling burst release of payloads by disrupting these vesicle membranes. In this regard, external stimuli such as pH, temperature and light are often used. One additional stimulus that is of interest to several researchers involves reactive oxygen species (ROS).

These ROS are routinely generated in living organisms and are essential for maintaining a balance in several physiological processes. It is also well known in the literature that ROS levels are usually much higher in tumor microenvironments than in normal tissues. Thus, if vesicle membranes responsive to ROS can be developed, the system could potentially be useful in cancer treatment. By utilizing this idea, we developed low-cost, simple, ROS responsive catanionic vesicle containers made from commercially available surfactants. Especially, we use a light and ROS responsive cationic molecule that is a commonly used photoinitiator and a photo-acid generator. When exposed to ROS or when irradiated with ultraviolet light (UV) or when heated to a higher temperature, it converts to a more hydrophilic structure or loses its charge. In turn, the vesicles are converted into micelles due to an increase in the critical packing parameter or loss of ionic interactions, thereby ensuring burst release of contents. Such stable, multi-responsive vesicles are desirable in many applications.