Mannan-decorated pathogen-like polymeric nanoparticles as nanovaccine carriers for eliciting superior anticancer immunity

Using nanotechnology for cancer vaccine design holds great promise because of the intrinsic feature of nano particles in being captured by antigen-presenting cells (APCs). However, there are still obstacles in current nanovaccine systems in achieving efficient tumor therapeutic effects, which could partially be attributed to the unsatisfactory vaccine carrier design. Herein, we report a mannan-decorated pathogen-like polymeric nano particle as a protein vaccine carrier for eliciting robust anticancer immunity. This nanovaccine was constructed as a core-shell structure with mannan as the shell, polylactic acid-polyethylenimine (PLA-PEI) assembled nanoparticle as the core, and protein antigens and Toll-like receptor 9 (TLR9) agonist CpG absorbed onto the PLA-PEI core via electrostatic interactions. Compared to other hydrophilic materials, mannan decoration could greatly enhance the lymph node draining ability of the nanovaccine and promote the capturing by the CD8(+) dendritic cells (DCs) in the lymph node, while PLA-PEI as the inner core could enhance antigen endosome escape thus promoting the antigen cross-presentation. In addition, mannan itself as a TLR4 agonist could synergize with CpG for maximally activating the DCs. Excitingly, we observed in several murine tumor models that using this nanovaccine alone could elicit robust immune response in vivo and result in superior anti-tumor effects with 50% of mice completely cured. This study strongly evidenced that mannan decoration and a rationally designed nanovaccine system could be quite robust in tumor vaccine therapy.

Automated summary

Using nanotechnology for cancer vaccine design holds great promise, but there are still obstacles to achieving efficient tumor therapeutic effects. This study reports the use of mannan-decorated polymeric nanoparticles as a protein vaccine carrier to elicit robust anticancer immunity. The nanovaccine showed enhanced lymph node draining ability and capturing by dendritic cells, as well as antigen endosome escape and antigen cross-presentation. Excitingly, the nanovaccine alone showed superior anti-tumor effects in murine tumor models.