상위피인용논문
- 조회559
Huu Thuy Trang Duong a 1, Yue Yin b 1, Thavasyappan Thambi a, Thanh Loc Nguyen a, V.H. Giang Phan a c, Min Sang Lee b, Jung Eun Lee b, Jaeyun Kim a, Ji Hoon Jeong b *, Doo Sung Lee a *
aSchool of Chemical Engineering, Theranostic Macromolecules Research Center, Sungkyunkwan University, Suwon 440-746, Republic of Korea
bSchool of Pharmacy, Theranostic Macromolecules Research Center, Sungkyunkwan University, Suwon 440-746, Republic of Korea
cFaculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam
1These authors contributed equally to this work.
*Corresponding author: correspondence to Ji Hoon Jeong or Doo Sung Lee
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.
논문정보
- Research article
- 2018년 12월 (BRIC 등록일 2023-08-22)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
- 120회 이상 인용된 논문
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