(165l) Triggered Release of Light-Responsive Model Prodrugs from Polymeric Core-Shell Nanocarriers Via UV Irradiation

Encapsulation of therapeutic agents into nanocarriers has the potential to improve the spatial and temporal control required for local administration of cancer drug delivery. To control local administration, many researchers have developed polymeric core-shell nanocarriers responsive to physiological triggers, such as pH, oxidation potential, or enzymatic degradation. Lately, nanocarriers responsive to external stimuli are becoming increasingly popular as they offer a higher degree of control. Of the external modalities, light is the least invasive due to its remote modulation and easy manipulation by controlling wavelength, intensity, and duration. Light-responsive nanocarriers are typically fitted with light sensitive moieties that respond to wavelengths within the UV range. Release of core material from constructs happens by disruption of nanocarriers through a variety of light-induced mechanisms. However, one avenue yet to be explored is the encapsulation of light-cleavable prodrug constructs within nanocarriers. Here, we present a novel polymeric core-shell nanocarrier drug delivery vehicle and show the triggered release of model drug constructs via UV irradiation. Prodrug constructs are based around the o-hydroxycinnamic acid platform because of its intrinsic nonfluorescence and capability of absorbing within the UV range to release small alcohols and fluorescent co-product. To show the versatility of the platform, we covalently link a variety of chemistries to form model prodrug constructs. Subsequent UV irradiation of the model prodrugs show the release of model drug, and fluorescent co-product used as a quantification tool for drug release. Lastly, we encapsulated the model prodrugs in polymeric nanocarriers and illuminated via UV irradiation to demonstrate controlled light-triggered release of fluorescent reporter and model drug out of the nanocarrier.