Peptide-based neoantigen vaccines hold tremendous potential
for
personalized tumor immunotherapy. However, effective delivery and
controllable release of antigen peptides remain major challenges in
stimulating robust and sustained immune responses. Programmable DNA
nanodevices provide accurate fixed positions for antigens, which are
convenient for the calculation of clinical dosage, and hold great
potential as precise carriers. Here, a peptide–nucleic acid
conjugate was prepared, which was driven by a propargyl sulfonium-based
efficient and reversible bio-orthogonal reaction under weakly alkaline
conditions, and folded into regular DNA nanodevice vaccines. The well-defined
nanoplatform not only exhibits outstanding stability in serum, satisfactory
safety, and effective internalization by antigen-presenting cells
(RAW264.7 and BMDCs) but also obviously enhances cytokine (TNF-α,
IL-6, and IL-12) secretion for further immune response. In
vivo, the nanovaccine cooperating with OVA model antigens
and CpG adjuvants stimulated an antigen-specific CD8+T
cell response, significantly preventing the lung metastases of melanoma.
In the B16-OVA tumor-bearing model, the growth inhibition rate of
melanoma reached up to 50%. Similarly, the DNA nanodevice with neoantigen
induced up to a maximum degree of complete MC-38 tumor regression
in 80% of mice, possibly owing to antigen peptide reversible release
driven by sulfonium and further cross-presentation. In brief, this
study demonstrates that DNA nanodevices with sulfonium centers can
provide a precise, biocompatible, and effective co-delivery vaccine
platform for tumor immunotherapy and prevention.
Visible-light-mediated methods were heavily studied as a useful tool for cysteine-selective bio-conjugation; however, many current methods suffer from bio-incompatible reaction conditions and slow kinetics. To address these challenges, herein, we...
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