Efficient lymph node-targeted delivery of personalized cancer vaccines with reactive oxygen species-inducing reduced graphene oxide nanosheets

James J. Moon, Cheng Xu, Hao Hong, Yonghyun Lee, Kyung Soo Park, Mingjiao Sun, Tianrui Wang, Marisa E. Aikins, Yao Xu

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)13268-13278
Number of pages11
JournalACS Nano
Volume14
Issue number10
DOIs
StatePublished - 27 Oct 2020

Bibliographical note

Publisher Copyright:
© 2020 American Chemical Society.

Keywords

  • Cancer immunotherapy
  • Cancer vaccine
  • Nanosheet
  • Positron emission tomography
  • Reduced graphene oxide

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