Sequential Barrier Navigation by Yeast β-Glucan-Engineered Liposomal Nanovaccines Potentiates Oral Melanoma Immunotherapy.
- 1Department of Pharmacy, Shandong Medical and Pharmaceutical University Hospital, Shandong Medical and Pharmaceutical University, Binzhou, Shandong, 256603, People's Republic of China.
- 2Department of Biochemistry and Molecular Biology, Shandong Medical and Pharmaceutical University, Yantai, Shandong, 264003, People's Republic of China.
Abstract
Purpose
Orally delivered protein antigens face gastrointestinal degradation and inefficient transport through mucus, across the intestinal epithelium, and into antigen-presenting cells (APCs). To address these barriers, we developed YGB@OVA/PBA-C-LIPs, an ovalbumin (OVA)-loaded cationic liposomal nanovaccine coated with yeast β-glucan (YGB) and functionalized with phenylboronic acid (PBA).Methods
We characterized the physicochemical properties of YGB@OVA/PBA-C-LIPs and evaluated their mucus and epithelial transport, macrophage uptake, OVA cross-presentation, and immune activation in vitro. Laminarin competition was used to assess β-glucan-sensitive uptake. Gastrointestinal residence, immune responses, antitumor activity, and tolerability were examined after oral administration to B16-OVA-bearing mice.Results
YGB@OVA/PBA-C-LIPs averaged 127.5 ± 0.8 nm in diameter and had an OVA encapsulation efficiency of 83.17 ± 1.98%, with no marked size increase over 12 days at 4 °C. They improved transport through a simulated mucus layer and across the Caco-2/Raji B model and increased RAW264.7 macrophage uptake; laminarin attenuated this advantage, supporting a β-glucan-sensitive component of uptake. The formulation also increased surface CD80 and H-2Kb-SIINFEKL levels in DC2.4 cells and IFN-γ release in DC2.4-splenocyte co-cultures. After a single oral dose, the Cy7-labeled formulation remained detectable in the abdomen at 72 h. Repeated dosing reduced tumor weight by 75.0% versus untreated tumor-bearing controls (0.36 ± 0.11 versus 1.44 ± 0.23 g) and increased serum OVA-specific IgG reactivity to 3.8 times the control value. Major-organ histology showed no evident abnormalities.Conclusion
The YGB/PBA dual-functionalized formulation combined gastrointestinal protection and mucosal transport with enhanced antigen presentation by APCs, improving immune responses and tumor control in the B16-OVA model. Validation with clinically relevant tumor antigens is needed to establish broader therapeutic relevance.
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BibTeX
@article{wu2026sequential,
title = {{Sequential Barrier Navigation by Yeast β-Glucan-Engineered Liposomal Nanovaccines Potentiates Oral Melanoma Immunotherapy.}},
author = {Dongyang Wu and Chenyang Jiang and Hui Li and Kairui Zhu and Wenyan Liu and Yang Guo and Weili Liu and Rui Yan and Zuoyuan Liang and Xiaoke Liu and Zhixin Zhao and Hongfang Sun and Yan Liang},
journal = {International journal of nanomedicine},
year = {2026},
month = oct,
doi = {10.2147/ijn.s631311},
url = {https://europepmc.org/article/MED/42903945},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Sequential Barrier Navigation by Yeast β-Glucan-Engineered Liposomal Nanovaccines Potentiates Oral Melanoma Immunotherapy.
AU - Dongyang Wu
AU - Chenyang Jiang
AU - Hui Li
AU - Kairui Zhu
AU - Wenyan Liu
AU - Yang Guo
AU - Weili Liu
AU - Rui Yan
AU - Zuoyuan Liang
AU - Xiaoke Liu
AU - Zhixin Zhao
AU - Hongfang Sun
AU - Yan Liang
PY - 2026
DA - 2026/10/16
JO - International journal of nanomedicine
DO - 10.2147/ijn.s631311
UR - https://europepmc.org/article/MED/42903945
AB - Purpose Orally delivered protein antigens face gastrointestinal degradation and inefficient transport through mucus, across the intestinal epithelium, and into antigen-presenting cells (APCs). To address these barriers, we developed YGB@OVA/PBA-C-LIPs, an ovalbumin (OVA)-loaded cationic liposomal nanovaccine coated with yeast β-glucan (YGB) and functionalized with phenylboronic acid (PBA).Methods We characterized the physicochemical properties of YGB@OVA/PBA-C-LIPs and evaluated their mucus and epithelial transport, macrophage uptake, OVA cross-presentation, and immune activation in vitro. Laminarin competition was used to assess β-glucan-sensitive uptake. Gastrointestinal residence, immune responses, antitumor activity, and tolerability were examined after oral administration to B16-OVA-bearing mice.Results YGB@OVA/PBA-C-LIPs averaged 127.5 ± 0.8 nm in diameter and had an OVA encapsulation efficiency of 83.17 ± 1.98%, with no marked size increase over 12 days at 4 °C. They improved transport through a simulated mucus layer and across the Caco-2/Raji B model and increased RAW264.7 macrophage uptake; laminarin attenuated this advantage, supporting a β-glucan-sensitive component of uptake. The formulation also increased surface CD80 and H-2Kb-SIINFEKL levels in DC2.4 cells and IFN-γ release in DC2.4-splenocyte co-cultures. After a single oral dose, the Cy7-labeled formulation remained detectable in the abdomen at 72 h. Repeated dosing reduced tumor weight by 75.0% versus untreated tumor-bearing controls (0.36 ± 0.11 versus 1.44 ± 0.23 g) and increased serum OVA-specific IgG reactivity to 3.8 times the control value. Major-organ histology showed no evident abnormalities.Conclusion The YGB/PBA dual-functionalized formulation combined gastrointestinal protection and mucosal transport with enhanced antigen presentation by APCs, improving immune responses and tumor control in the B16-OVA model. Validation with clinically relevant tumor antigens is needed to establish broader therapeutic relevance.
SN - 1176-9114
SN - 1178-2013
ER -