Proton-driven transformable nanovaccine for cancer immunotherapy.
Nat Nanotechnol
; 15(12): 1053-1064, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-33106640
ABSTRACT
Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies. Here, we present a proton-driven nanotransformer-based vaccine, comprising a polymer-peptide conjugate-based nanotransformer and loaded antigenic peptide. The nanotransformer-based vaccine induces a strong immune response without substantial systemic toxicity. In the acidic endosomal environment, the nanotransformer-based vaccine undergoes a dramatic morphological change from nanospheres (about 100 nanometres in diameter) into nanosheets (several micrometres in length or width), which mechanically disrupts the endosomal membrane and directly delivers the antigenic peptide into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. The nanotransformer-based vaccine effectively inhibits tumour growth in the B16F10-OVA and human papilloma virus-E6/E7 tumour models in mice. Moreover, combining the nanotransformer-based vaccine with anti-PD-L1 antibodies results in over 83 days of survival and in about half of the mice produces complete tumour regression in the B16F10 model. This proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cancer Vaccines
/
Delayed-Action Preparations
/
Nanospheres
/
Antigens
/
Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Nat Nanotechnol
Year:
2020
Document type:
Article
Affiliation country:
China