Localized drug delivery holds great promise as a means of circumventing traditional chemotherapy side effects associated with high toxicity and prolonged treatments. Nanosized carriers (i.e., with diameters <100 nm) can often accumulate in tumor cells, yet it remains a challenge to design such carriers that are at the same time durable (to survive delivery) and degradable (to release the payload once inside cells). In the present study, photoresponsive catanionic vesicles are utilized to codeliver Bcl-2 siRNA and paclitaxel into MDA-MB-231 human breast cancer cells. These vesicles, which form spontaneously upon simple mixing of an azobenzene-based cationic surfactant and a conventional anionic surfactant, disassociate into free surfactants upon UV illumination. This allows for phototriggered release of the coloaded therapeutics following cellular uptake, which is shown to enhance both cell death and protein suppression. Dynamic light scattering, zeta potential, small-angle neutron scattering, and fluorescence spectroscopy measurements are utilized to determine the optimal vesicle size, charge, bilayer thickness, and concentration for encapsulation and uptake. Cell viability, flow cytometry, and confocal microscopy are used to demonstrate safe and effective dosages, whereas knockdown of Bcl-2 protein expression was confirmed by Western blots.

β-Glucosidases catalyze the hydrolysis of cellobiose to glucose, which is often the rate-limiting step in the conversion of cellulose into fermentable sugars during bioethanol production. Thus, the structure and function of β-glucosidase from Aspergillus niger were examined in response to a photoresponsive azobenzene-based surfactant (4ethyl-4′(trimethylamino-butoxy)azobenzene bromide, azoTAB) as a means to enhance the enzyme activity. Light and neutron scattering data indicate that pure β-glucosidase exists as dimers or higher aggregates in solution that are progressively converted to monomers with an increasing azoTAB concentration. This transition is accompanied by a 60% increase in catalytic activity. In contrast, the enzyme is simply deactivated in the presence of conventional straight-chain hydrocarbon surfactants. Shape-reconstructed images obtained from SANS data demonstrate that azoTAB causes selective unfolding in the α/β sandwich domain that comprises the crystallographic dimer interface, consistent with the observed transition to monomers. Furthermore, this domain forms one side of a long cleft that begins at the active site and facilitates the nonproductive binding of substrate or longer oligosaccharides, which at times can block the active site. Indeed, kinetic data indicate that the azoTAB-induced increase in β-glucosidase activity is a result of diminished substrate inhibition, thus providing a unique means of obtaining glucose-tolerant β-glucosidases.