Self-Assembled Injectable Peptide Hydrogels Capable of Triggering Antitumor Immune Response

Abstract

Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and antitumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures, and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly peptide (poly-l-lysine, PLL). Electrostatic coupling between PLL and a self-assembling dipeptide (Fmoc-FF) provides a smart switch to enable the fibrous hydrogels to be shear-thinning and self-healing, thus leading to the formation of supramolecular hydrogels with rheological properties suitable for injection. The latter can be flexibly adjusted by merely varying the concentration or the molecular weight of the polypeptide to satisfy a variety of requirements in biological applications. The hydrogels, consisting of helical nanofibers stabilized with disulfide bonds, are prepared and further injected for antitumor therapy. The results demonstrate that the helical fibrous hydrogel, without the addition of antigens, immune regulatory factors, and adjuvants, can activate T cell response and efficiently suppress tumor growth. Therefore, injectable hydrogels self-assembled by a combination of small peptides and biomacromolecules present a great potential for biomedical applications, especially for development of a new type of immuno-responsive materials toward antitumor therapy.