Oxidation-Sensitive Dextran-Based Polymer with Improved Processability through Stable Boronic Ester Groups

Particulate immunotherapy holds promise to vaccinate or treat a broad array of illnesses, including cancer, infectious diseases, and autoimmune disorders. The rate of antigen release from nano/microparticles (MPs) can impact both the type and quality of the immune response they elicit. The lysosomes of antigen-presenting cells are highly oxidizing. Thus, an oxidation-sensitive vehicle could enable a significant advancement in effective MP immunotherapy. One promising class of materials being developed toward this end is aryl-boronate-modified dextran polymers. The boronic esters used for oxidation-sensitive materials and sensors are typically made using pinacol (Pin) as a diol. However, Pin-based aryl-boronate-modified polymers are capable of transesterifying with biogenic diols, which can lead to undesirable interactions and poor material properties. To solve this, pinanediol (PD) was used in place of Pin in the synthesis of an aryl-boronate-modified dextran polymer (PDB-Dex), yielding a highly stable boronic ester. This modified dextran reverses its water solubility as desired, and improves on Pin-based materials by maintaining its solubility in organic solvents. MPs could be prepared by emulsion, nanoprecipitation, and electrospray techniques. The hydrogen peroxide-triggered degradation of microparticles was quantified colorimetrically, and the mechanism was probed using H-1 NMR. Preliminary in vitro studies show low cytotoxicity and the ability to deliver an immunostimulatory agent.