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Sci Rep. 2016 Dec 2;6:38348. doi: 10.1038/srep38348.

In vivo stepwise immunomodulation using chitosan nanoparticles as a platform nanotechnology for cancer immunotherapy.

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Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
Department of Dental Hygiene, Hanseo University, Seosan 31962, South Korea.
Department of Convergence Medicine, University of Ulsan College of Medicine &Asan Institute for Life Sciences, Asan Medical Center, Seoul 055-05, South Korea.
SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon 25-2, South Korea.
Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul 143-747, South Korea.
Department of Obstetrics and Gynecology, Samsung Medical Center, Sunkyunkwan University School of Medicine, Seoul 06531, South Korea.
Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, South Korea.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, South Korea.
Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas M.D. Anderson Cancer Center, Texas, USA.
Department of Cancer Biology, the University of Texas M.D. Anderson Cancer Center, Texas, USA.
Center for RNA Interference and Non-coding RNA, The University of Texas M.D. Anderson Cancer Center, Texas, USA.


Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes. We developed CH-NPs encapsulating ovalbumin (OVA) as a model antigen and poly I:C as the adjuvant in an ionic complex. These CH-NPs showed increased in vivo intracellular delivery to the DCs in comparison with controls after injection into tumor-bearing mice, and promoted DC maturation, leading to emergence of antigen-specific cytotoxic CD8+ T cells. Finally, the CH-NPs showed significantly greater antitumor efficacy in EG.7 and TC-1 tumor-bearing mice compared to the control (p < 0.01). Taken together, these data show that the CH-NP platform can be used as an immune response modulatory vaccine for active cancer immunotherapy without ex vivo manipulation, thus resulting in increased anticancer efficacy.

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