Dendritic Cell-Targeted pH-Responsive Extracellular Vesicles for Anticancer Vaccinationopen access
- Authors
- Lee, Hyuk; Park, Hongsuk; Yu, Hyeong Sup; Na, Kun; Oh, Kyung Taek; Lee, Eun Seong
- Issue Date
- Feb-2019
- Publisher
- MDPI
- Keywords
- extracellular vesicles; pH-responsive; dendritic cells; toll-like receptor 4 signaling; anticancer vaccine
- Citation
- PHARMACEUTICS, v.11, no.2
- Journal Title
- PHARMACEUTICS
- Volume
- 11
- Number
- 2
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/18295
- DOI
- 10.3390/pharmaceutics11020054
- ISSN
- 1999-4923
1999-4923
- Abstract
- Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), 3-(diethylamino)propylamine (DEAP), monophosphoryl lipid A (MPLA), and mucin 1 peptide (MUC1), referred to as HDEA@EVAT. HDEA@EVAT potentiated the differentiation and maturation of monocytes into dendritic cells (DCs) and the priming of CD8(+) T-cells for cancer therapy. MPLA and HA enabled HDEA@EVAT to interact with the toll-like receptor 4 and the CD44 receptor on DCs, followed by endosomal escape, owing to the protonation of pH-sensitive DEAP on the EV in conjunction with MUC1 release. The MUC1 was then processed and presented to DCs to activate CD8(+) T-cells for additional anticancer-related immune reactions. Our findings support the anticancer vaccine activity by which HDEA@EVAT expedites the interaction between DCs and CD8(+) T-cells by inducing DC-targeted maturation and by presenting the cancer-associated peptide MUC1.
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