Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy

Guizhi Zhu, Lei Mei, Harshad D. Vishwasrao, Orit Jacobson, Zhantong Wang, Yijing Liu, Bryant C. Yung, Xiao Fu, Albert Jin, Gang Niu, Qin Wang, Fuwu Zhang (), Hari Shroff and Xiaoyuan Chen ()
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Guizhi Zhu: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Lei Mei: College of Agriculture and Natural Resources, University of Maryland
Harshad D. Vishwasrao: Advanced Imaging and Microscopy Resource, NIH
Orit Jacobson: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Zhantong Wang: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Yijing Liu: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Bryant C. Yung: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Xiao Fu: Laboratory of Cellular Imaging and Macromolecular Biophysics, NIBIB, NIH
Albert Jin: Laboratory of Cellular Imaging and Macromolecular Biophysics, NIBIB, NIH
Gang Niu: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Qin Wang: College of Agriculture and Natural Resources, University of Maryland
Fuwu Zhang: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Hari Shroff: Advanced Imaging and Microscopy Resource, NIH
Xiaoyuan Chen: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs. CpG and shRNA in iDR-NCs synergistically activate APCs for sustained antigen presentation. Remarkably, iDR-NC/neoantigen nanovaccines elicit 8-fold more frequent neoantigen-specific peripheral CD8+ T cells than CpG, induce T cell memory, and significantly inhibit the progression of neoantigen-specific colorectal tumors. Collectively, iDR-NCs represent potential DNA/RNA/peptide triple-co-delivery nanocarriers and synergistic tumor immunotherapeutic nanovaccines.

Date: 2017
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DOI: 10.1038/s41467-017-01386-7

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