Conventional vaccine adjuvants primarily rely on molecular binding and biochemical stimulation to activate immune responses, which often leads to limited efficacy in elderly or low-responsive populations. How to introduce physical regulation into immune activation remains an open challenge.
Now, a research team led by Prof. XIA Yufei from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences has demonstrated that redesigning aluminum adjuvants into a deformable, three-dimensional mechanical interface can significantly enhance immune activation.
The researchers constructed aluminum-stabilized Pickering emulsions (ASPEs) that enable dendritic cells (DCs) to actively sense interfacial mechanical cues, thereby amplifying immune responses.
Unlike conventional particulate adjuvants with limited membrane contact, ASPE droplets deform upon contact with DC membranes, increasing the interfacial contact area and delivering controllable mechanical stress.
By tuning the crystallinity of aluminum nanoparticles, the interfacial stiffness can be precisely regulated, allowing graded mechanical stimulation. Stronger mechanical cues directly activate the mechanosensitive ion channel PIEZO1, trigger Ca²⁺ influx, and promote antigen cross-presentation.
When combined with the TLR4 agonist monophosphoryl lipid A (MPLA), the ASPE platform achieves synergistic mechano-biochemical activation. Compared with the clinically used Alum+MPLA formulation, ASPE-M induces stronger DC maturation, enhanced Th1-biased immunity, and robust CD8⁺ T-cell responses.
These effects are pronounced in aged mouse models and significantly improve therapeutic outcomes in dendritic cell-based melanoma immunotherapy, especially when combined with PD-1 blockade.
Overall, this work establishes interfacial mechanics as a critical and programmable dimension of immune regulation, complementary to traditional biochemical signaling. These findings provide a new strategy for vaccine and immunotherapy design, with particular promise for improving immune efficacy in aging and immunocompromised populations.
The study was published in Cell Biomaterials on December 10.
Interfacial mechano-biochemical dual signaling potentiates immune activation by Aluminum-stabilized Pickering emulsions (Image by IPE)
