Duong, Huu Thuy Trang; Yin, Yue; Thambi, Thavasyappan; Nguyen, Thanh Loc; Giang Phan, V H; Lee, Min Sang; Lee, Jung Eun; Kim, Jaeyun; Jeong, Ji Hoon; Lee, Doo Sung
Biomaterials
2018Sep ; 185 ( 1 ) :13-24.
PMID : 30216806
ÀúÀÚ »ó¼¼Á¤º¸
Duong, Huu Thuy Trang -
Yin, Yue -
Thambi, Thavasyappan -
Nguyen, Thanh Loc -
Giang Phan, V H -
Lee, Min Sang -
Lee, Jung Eun -
Kim, Jaeyun -
Jeong, Ji Hoon -
Lee, Doo Sung -
ABSTRACT
Despite the tremendous potential of DNA-based cancer vaccines, their efficacious delivery to antigen presenting cells to stimulate both humoral and cellular response remains a major challenge. Although electroporation-based transfection has improved performance, an optimal strategy for safe and pain-free vaccination technique remains elusive. Herein, we report a smart DNA vaccine delivery system in which nanoengineered DNA vaccine was laden on microneedles (MNs) assembled with layer-by-layer coating of ultra-pH-responsive OSM-(PEG-PAEU) and immunostimulatory adjuvant poly(I:C), a synthetic double stranded RNA. Transcutaneous application of MN patches onto the mice skin perforate the stratum corneum with minimal cell damage; subsequent disassembly at the immune-cell-rich epidermis/dermis allows the release of adjuvants and DNA vaccines, owing to the ultra-sharp pH-responsive nature of OSM-(PEG-PAEU). The released adjuvant and DNA vaccine can enhance dendritic cell maturation and induce type I interferons, and thereby produce antigen-specific antibody that can achieve the antibody-dependent cell-mediated cytotoxicity (ADCC) and CD8(+) T cell to kill cancer cells. Strikingly, transcutaneous application of smart vaccine formulation in mice elicited 3-fold greater frequencies of Anti-OVA IgG1 serum antibody and 3-fold excess of cytotoxic CD8(+) T cell than soluble DNA vaccine formulation. As a consequence, the formulation rejected the murine B16/OVA melanoma tumors in C57BL/6 mice through the synergistic activation of antigen-specific ADCC and cytotoxic CD8(+) T cells. The maneuvered use of vaccine and adjuvant poly(I:C) in MNs induces humoral and cellular immunity, which provides a promising vaccine technology that shows improved efficacy, compliance, and safety. CI - Copyright ??2018. Published by Elsevier Ltd.
keyword
Cancer immunotherapy; DNA vaccines; Microneedles; Poly(I:C); pH-sensitive copolymers
¸µÅ©