期刊
BIOMATERIALS
卷 206, 期 -, 页码 25-40出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.03.012
关键词
Lipid-hybrid polymersomes; Mannose-receptor targeting; Antigen delivery; Imiquimod; Monophosphoryl lipid A; Cancer vaccine
资金
- National Natural Science Foundation of China [81571793, 81671806, 51103180, 81100100]
- CAMS Initiative for Innovative Medicine [2017-I2M-3-020, 2017-I2M-4-001]
- Tianjin Municipal Natural Science Foundation [15JCZDJC38300]
Exploiting Toll-like receptor (TLR) agonists or their certain combinations can enhance the immune potency of subunit vaccine. Nevertheless, the design of co-delivery systems which can act in a synergistic and spatio-temporal way to achieve effective and durable specific immune response is still challenging. Here we fabricated mannose-functionalized lipid-hybrid polymersomes (MAN-IMO-PS) for co-delivery of ovalbumin antigen both inside the inner core and outside the lipid layer, TLR7/8 agonist imiquimod within the hydrophobic membrane, TLR4 agonist monophosphoryl lipid A in the lipid layer as programmed nanovaccine to synergistically activate immune responses for improving vaccine efficacy. After efficiently internalized by dendritic cells via mannose targeting and TLR4 ligating, MAN-IMO-PS significantly enhanced cross-presentation and cytokine production. In addition, MAN-IMO-PS showed depot effect at the injection site and enhanced migration to draining lymph nodes. Mice immunized with MAN-IMO-PS elicited greater lymphocyte activation, CD4(+) and CD8(+) T cell response, effector cytokines secretion, and induced Th-1 biased humoral responses. More importantly, prophylactic vaccination by MAN-IMO-PS significantly delayed tumor occurrence, suppressed tumor growth with prolonged survival, and achieved long-term immune effect. The present study demonstrates a rationally designed nanovaccine for combining antigen, different TLR agonists, and targeting moiety in a programmed manner to induce synergistic antitumor immune response.
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