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. ; The authors thank Prof. Karen Smeets (Biodiversity and Toxicology Group, Centre for Environmental Sciences, UHasselt) for providing access to the LSM900 confocal microscope, Birte Luyck for acquiring TEM images, and Dr. Annelies Sels for supporting elemental analysis. Sourav Nayak is funded by the BOF Special Research Fund of Hasselt University (BOF21OWB04). Esther Wolfs and Anitha Ethirajan received funding from the Hasselt University large BOF project program (BOF21GP08). Esther Wolfs is funded by the ...