RESUMEN
mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with ß-glucans (ßGlus), a potential adjuvant for vaccines, encapsulated within LNPs (ßGlus/mRNA@LNPs). The ßGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, ßGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral ßGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration.
RESUMEN
The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration.
