Efficient Lymph Node-Targeted Delivery of Personalized Cancer Vaccines with Reactive Oxygen Species-Inducing Reduced Graphene Oxide Nanosheets
- 주제(키워드) reduced graphene wade , nanosheet , cancer vaccine , cancer ammunotherapy , positron emission tomography
- 주제(기타) Chemistry, Multidisciplinary
- 주제(기타) Chemistry, Physical
- 주제(기타) Nanoscience & Nanotechnology
- 주제(기타) Materials Science, Multidisciplinary
- 설명문(일반) [Xu, Cheng; Lee, Yonghyun; Sun, Mingjiao; Wang, Tianrui; Aikins, Marisa E.; Xu, Yao; Moon, James J.] Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA; [Xu, Cheng; Lee, Yonghyun; Park, Kyung Soo; Aikins, Marisa E.; Xu, Yao; Moon, James J.] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA; [Hong, Hao] Nanjing Univ, Sch Med, Nanjing 210093, Jiangsu, Peoples R China; [Lee, Yonghyun] Ewha Womans Univ, Grad Sch, Coll Pharm & Pharm, Dept Pharm, Seoul 03760, South Korea; [Park, Kyung Soo; Moon, James J.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
- 등재 SCIE, SCOPUS
- OA유형 Green Accepted
- 발행기관 AMER CHEMICAL SOC
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175119
- 본문언어 영어
- Published As http://dx.doi.org/10.1021/acsnano.0c05062
- PubMed https://pubmed.ncbi.nlm.nih.gov/32902245
초록/요약
Therapeutic cancer vaccines require robust cellular immunity for the efficient killing of tumor cells, and recent advances in neoantigen discovery may provide safe and promising targets for cancer vaccines. However, elicitation of T cells with strong antitumor efficacy requires intricate multistep processes that have been difficult to attain with traditional vaccination approaches. Here, a multifunctional nanovaccine platform has been developed for direct delivery of neoantigens and adjuvants to lymph nodes (LNs) and highly efficient induction of neoantigen-specific T cell responses. A PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20-30 nm in diameter) is a highly modular and biodegradable platform for facile preparation of neoantigen vaccines within 2 h. RGO-PEG exhibits rapid, efficient (15-20% ID/g), and sustained (up to 72 h) accumulation in LNs, achieving >100-fold improvement in LN-targeted delivery, compared with soluble vaccines. Moreover, RGO-PEG induces intracellular reactive oxygen species in dendritic cells, guiding antigen processing and presentation to T cells. Importantly, a single injection of RGO-PEG vaccine elicits potent neoantigen-specific T cell responses lasting up to 30 days and eradicates established MC-38 colon carcinoma. Further combination with anti-PD-1 therapy achieved great therapeutic improvements against B16F10 melanoma. RGO-PEG may serve a powerful delivery platform for personalized cancer vaccination.
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