TY - JOUR
T1 - Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells
AU - Phanse, Yashdeep
AU - Carrillo-Conde, Brenda R.
AU - Ramer-Tait, Amanda E.
AU - Roychoudhury, Rajarshi
AU - Pohl, Nicola L.B.
AU - Narasimhan, Balaji
AU - Wannemuehler, Michael J.
AU - Bellaire, Bryan H.
N1 - Funding Information:
B.N. and M.J.W. acknowledge financial support from the US Department of Defense – Office of Naval Research (ONR Award No. N00014-06-1-1176 ). B.N., M.J.W. and N.P. also acknowledge financial support from the US Army Medical Research and Materiel Command (Grant No. W81XWH-10-1-0806 ). B.H.B. acknowledges startup funds provided by Iowa State University College of Veterinary Medicine and the Office of Biotechnology . B.N. and M.J.W. acknowledge financial support from the Health Resources and Services Administration (Grant No. C76HF19578 ).
PY - 2013/11
Y1 - 2013/11
N2 - Innovative vaccine delivery platforms can facilitate the development of effective single-dose treatment regimens to control emerging and re-emerging infectious diseases. Polyanhydride microparticles are promising vaccine delivery vehicles due to their ability to stably maintain antigens, provide tailored release kinetics and function as adjuvants. A major obstacle for the use of microparticle-based vaccines, however, is their limited uptake by dendritic cells (DCs). In this study, we functionalized the microparticle surface with di-mannose in order to target C-type lectin receptors (CLRs) on DCs. Polyanhydride particles based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy) hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were evaluated. Co-incubation of di-mannose-functionalized microparticles up-regulated the expression of CLRs on DCs. More importantly, di-mannose functionalization increased the uptake, as measured by the percentage of cells internalizing particles. The uptake of CPH:SA microparticles increased ∼20-fold, from 0.82% (non-functionalized) to 20.2%, and internalization of CPTEG:CPH microparticles increased ∼7-fold from 1.35% (non-functionalized) to 9.3% upon di-mannose functionalization. Both di-mannose-functionalized and non-functionalized particles trafficked to lysosomes. Together, these studies demonstrate that employing rational vaccine design principles, such as the targeting of CLRs on antigen-presenting cells, can enhance delivery of encapsulated antigens and potentially induce a more robust adaptive immune response.
AB - Innovative vaccine delivery platforms can facilitate the development of effective single-dose treatment regimens to control emerging and re-emerging infectious diseases. Polyanhydride microparticles are promising vaccine delivery vehicles due to their ability to stably maintain antigens, provide tailored release kinetics and function as adjuvants. A major obstacle for the use of microparticle-based vaccines, however, is their limited uptake by dendritic cells (DCs). In this study, we functionalized the microparticle surface with di-mannose in order to target C-type lectin receptors (CLRs) on DCs. Polyanhydride particles based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy) hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were evaluated. Co-incubation of di-mannose-functionalized microparticles up-regulated the expression of CLRs on DCs. More importantly, di-mannose functionalization increased the uptake, as measured by the percentage of cells internalizing particles. The uptake of CPH:SA microparticles increased ∼20-fold, from 0.82% (non-functionalized) to 20.2%, and internalization of CPTEG:CPH microparticles increased ∼7-fold from 1.35% (non-functionalized) to 9.3% upon di-mannose functionalization. Both di-mannose-functionalized and non-functionalized particles trafficked to lysosomes. Together, these studies demonstrate that employing rational vaccine design principles, such as the targeting of CLRs on antigen-presenting cells, can enhance delivery of encapsulated antigens and potentially induce a more robust adaptive immune response.
KW - C-type lectin receptors
KW - Di-mannose
KW - Microparticles
KW - Polyanhydride
KW - Targeted vaccines
KW - Uptake
UR - http://www.scopus.com/inward/record.url?scp=84885086026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885086026&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2013.06.024
DO - 10.1016/j.actbio.2013.06.024
M3 - Article
C2 - 23796408
AN - SCOPUS:84885086026
VL - 9
SP - 8902
EP - 8909
JO - Acta Biomaterialia
JF - Acta Biomaterialia
SN - 1742-7061
IS - 11
ER -