A research team led by Prof. LIANG XingJie from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences and Prof. LI Jinghong from Tsinghua University proposed a new strategy for constructing transformable nanocarriers to improve antigen delivery and cancer vaccination. This study was published in Nature nanotechnology. 

Cancer immunotherapy has become a powerful strategy for treating cancers. Cancer vaccine is one of the most promising immunotherapy techniques. However, the inducing of potent antitumor immunity by cancer vaccines is always restricted by insufficient cytosolic delivery and inadequate innate immune activation. 

In this study, the researchers presented a proton-driven nanotransformer-based vaccine (NTV).  

The nanotransformer is an amphiphilic polymer-peptide conjugate, which can self-assemble into nanospheres and antigenic peptide (AP) can be encapsulated in the nanostructure with a double-emulsion method. These nanospheres are stable at physiological pH value (pH 7.4).  

However, in the acidic endo/lysosomal environment (~pH 5.6), NTV undergoes a dramatic morphological change from nanospheres (~100 nm in diameter) into nanosheets (several micrometers in length or width). This morphological change leads to efficient endosomal membrane disruption by mechanical forces and allows effective cytosolic delivery of antigenic peptide. 

Moreover, the re-assembled nanosheets also activates the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome pathway. This feature contributes to antigen cross-presentation to CD8⁺ T cells.  

The researchers found that NTV effectively inhibits tumour growth in B16F10-OVA and human papilloma virus-E6/E7 tumour models. Additionally, combining tumor neoantigen-loaded NTV with anti-PD-L1 antibodies results in about 50% complete tumour regression and significantly prolonged mice survival in a melanoma model. 

The proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy.