Chiral Polypeptide Thermogels Induce Controlled Inflammatory Response as Potential Immunoadjuvants

The in vivo implanted biomaterials are known to induce inflammatory response and recruit immune cells, which could be used as robust adjuvants for immunotherapy. However, the degree of inflammatory response induced by the implanted biomaterials is hard to control. In this work, we reported the application of three kinds of thermogels from the polypeptide methoxy poly(ethylene glycol)–polyalanine (mPEG–PAla) with various chiralities to regulate the levels of inflammatory responses in vivo. The mPEG–PLAla (EG45LA28) and mPEG–PDAal (EG45DA27) thermogels exhibited comparable storage modulus (G′) and loss modulus (G″), both of which were about two times higher than the values of the racemic mPEG–PAla (EG45RA) thermogel. The component d-alanine in the polypeptide thermogels led to controlled tissue inflammation after subcutaneous injection, and the content of d-alanine could adjust the level of inflammation. The expression of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in subcutaneous tissue around the injected thermogel EG45DA27 were 3.62, 1.52, and 4.55 times the levels of those after EG45RA thermogel injection and 4.52, 7.38, and 7.96 times the levels of those after EG45LA28 injection, respectively. The results indicated that the chiral polypeptide thermogels could induce a controllable inflammatory response in vivo and exhibit great potential as an efficient adjuvant for immunotherapy.