Development and Characterization of a Nanoparticle-Based Oral Delivery System for Tumor-Associated Antigens (TAAs) (ECC Session)

Oral drug delivery of protein therapeutics has the potential to transform cancer immunotherapy by improving patient compliance and offering a needle-free alternative to traditional injectable treatments. However, effective oral delivery remains a significant challenge due to enzymatic degradation in the gastrointestinal (GI) tract and poor bioavailability, which limit the therapeutic efficacy of protein-based treatments. This study focuses on engineering a controlled-release nanoparticle formulation to enhance the oral bioavailability and delivery of tumor-associated antigens (TAAs) to stimulate an antitumor immune response.

We synthesized nanoparticles using acrylamide (AAM), N,N'-methylenebisacrylamide (BIS), ammonium persulfate (APS), and N,N,N',N'-tetramethylethylenediamine (TEMED), optimizing conditions to ensure stability and prevent aggregation. Characterization studies—including dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), mass spectrometry, and circular dichroism (CD)—confirmed successful nanoparticle formation with favorable size, morphology, and protein encapsulation.

Initially, bovine serum albumin (BSA) was used as a model protein to validate the encapsulation process and nanoparticle stability. The next phase of this study will replace BSA with tumor-associated antigens (TAAs) and evaluate bioavailability, immune response, and therapeutic potential in mouse models. Future work will further optimize oral bioavailability by incorporating mucoadhesive or pH-responsive coatings to enhance GI stability and absorption.

This work establishes a versatile, acrylamide-based nanoparticle platform for oral protein delivery, offering a stable encapsulation method for therapeutic proteins. By addressing key stability and absorption challenges, this system could be adapted for targeted cancer immunotherapies, oral vaccines, and other protein-based treatments, improving accessibility in resource-limited settings.