Reactive oxygen species responsive dextran-thioketal conjugate nanocarriers for the delivery of hydrophilic payloads

Dextran-thioketal conjugate (DTKC) nanocarrier responsive to endogenous as well as exogenous stimuli is developed for delivering hydrophilic payloads. First, water-soluble reactive oxygen species (ROS)-responsive DTKCs are synthesized and responsiveness to various ROS stimuli is studied. Next, different DTKC nanocarriers (NCs) loaded with the respective hydrophilic molecules - fluorescent dye (rhodamine B, RhoB), photosensitizer, PS (rose bengal, RB), and chemotherapeutic drug (doxorubicin hydrochloride, Dox) - are synthesized using inverse miniemulsion interfacial polymerization. All NCs exhibit nanocapsule morphology, and cargo dependent hydrodynamic diameters (166-194 nm) in water, an encapsulation efficiency between 79 and 91 %, and a drug loading content of about 11 %. RhoB-NCs and Dox-NCs exhibit time-dependent release upon exposure to different H₂O₂ concentrations and an enhanced release in conditioned medium collected from oral squamous cell carcinoma (OSCC) cells. Further, as a proof-of-concept, light-responsive payload release from PS loaded NCs via a cascade reaction is confirmed. The in vitro studies show that RhoB-NCs and RB-NCs are biocompatible while the Dox-NCs exhibit cytotoxic effects. Such dextran-based ROS-responsive NCs sensitive to endogenous (ROS rich environment) as well as exogenous (light in combination with a PS) stimuli are highly interesting to realize combination therapies, for instance combining a chemotherapeutic drug and a photosensitizer for application in photochemotherapy.