Leveraging polysaccharide-derived nanocarriers to open new horizons in oral vaccine activation

Oral vaccines represent a transformative approach in immunization, offering non-invasive administration, mucosal immune activation, and improved patient compliance. However, their clinical translation is hindered by multiple physiological barriers, such as gastric degradation, enzymatic hydrolysis, and inefficient antigen uptake in gut-associated lymphoid tissues. This review explores the emerging role of polysaccharide-derived nanocarriers, particularly those inspired by traditional Chinese medicine (TCM), in addressing these challenges. We discuss how these biocompatible and biodegradable materials can be engineered to enhance antigen stability, promote targeted delivery to Peyer's patches, and stimulate robust mucosal and systemic immune responses. Key design principles—such as bioadhesion, structural tunability, and immunomodulatory capacity—are highlighted across various carrier systems. Moreover, we examine multifunctional delivery strategies, including co-delivery of adjuvants, pH-responsive release, and mucoadhesive platforms. Special emphasis is placed on the potential integration of polysaccharide nanocarriers into next-generation oral mRNA and nucleic acid vaccine technologies. These insights underscore the promise of polysaccharide-based nanotechnology as a cornerstone for future oral vaccine platforms, paving the way for non-invasive, scalable, and immunologically effective vaccination strategies.