TY - JOUR
T1 - Co-delivery of antigen and dual agonists by programmed mannose-targeted cationic lipid-hybrid polymersomes for enhanced vaccination
AU - Zhu, Dunwan
AU - Hu, Chunyan
AU - Fan, Fan
AU - Qin, Yu
AU - Huang, Chenlu
AU - Zhang, Zhiming
AU - Lu, Lu
AU - Wang, Hai
AU - Sun, Hongfan
AU - Leng, Xigang
AU - Wang, Chun
AU - Kong, Deling
AU - Zhang, Linhua
N1 - Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Antigen delivery
KW - Cancer vaccine
KW - Imiquimod
KW - Lipid-hybrid polymersomes
KW - Mannose-receptor targeting
KW - Monophosphoryl lipid A
UR - http://www.scopus.com/inward/record.url?scp=85063606047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063606047&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2019.03.012
DO - 10.1016/j.biomaterials.2019.03.012
M3 - Article
C2 - 30925286
AN - SCOPUS:85063606047
SN - 0142-9612
VL - 206
SP - 25
EP - 40
JO - Biomaterials
JF - Biomaterials
ER -