Chiral Polypeptide Thermogels Induce Controlled Inflammatory Response as Potential Immunoadjuvants

Area of Science:

• Biomaterials Science
• Immunology
• Polymer Chemistry

Background:

• In vivo implanted biomaterials can trigger immune responses, making them potential adjuvants for immunotherapy.
• Controlling the inflammatory response induced by biomaterials is a significant challenge.
• Polypeptide thermogels present an opportunity to modulate these immune responses.

Purpose of the Study:

• To investigate the use of chiral polypeptide thermogels for regulating in vivo inflammatory responses.
• To assess the impact of varying d-alanine content on inflammation levels.
• To evaluate the potential of these thermogels as adjuvants in immunotherapy.

Main Methods:

• Synthesis of three types of methoxy poly(ethylene glycol)-polyalanine (mPEG-PAla) thermogels with different chiralities (EG45LA28, EG45DA27, EG45RA).
• Characterization of thermogel properties, including storage modulus (G') and loss modulus (G″).
• Subcutaneous injection of thermogels in vivo and subsequent measurement of inflammatory cytokine expression (TNF-α, IL-1β, IL-6).

Main Results:

• Chiral polypeptide thermogels, particularly those containing d-alanine (EG45DA27), induced controllable inflammatory responses.
• The d-alanine content directly correlated with the level of inflammation observed.
• Thermogel EG45DA27 significantly upregulated key inflammatory markers (TNF-α, IL-1β, IL-6) compared to racemic and l-alanine counterparts.
• EG45LA28 and EG45DA27 thermogels showed higher mechanical properties than the racemic EG45RA thermogel.

Conclusions:

• Chiral polypeptide thermogels provide a tunable platform for controlling in vivo inflammatory responses.
• The d-alanine component is crucial for modulating the inflammatory milieu.
• These thermogels demonstrate significant potential as effective adjuvants for enhancing immunotherapy outcomes.