A Supramolecular Approach to Develop New Soybean and Lupin Peptide Nanogels with Enhanced Dipeptidyl Peptidase IV (DPP-IV) Inhibitory Activity

Soy1 (IAVPTGVA) and Lup1 (LTFPGSAED), two peptides from soybean and lupin protein hydrolysis, have been singled out as dipeptidyl peptidase IV (DPP-IV) activity inhibitors in different model systems. However, their activity is affected by their instability toward intestinal proteases. Here, an innovative strategy based on nanogels was developed in order to increase both their stability and antidiabetic properties through encapsulation into the RADA16 peptide. The nanogel formation was stimulated by a solvent-triggered approach, allowing us to produce stable nanogels (G′ = 1826 Pa, stress-failure ≥50 Pa) with shear-thinning propensity. ThT binding assay, and ATR-FTIR spectroscopy experiments showed that nanogels self-aggregated into stable cross-β structures providing higher resistance against proteases (ex vivo experiments) and increased bioavailability of Soy1 and Lup1 peptides (in situ experiments on Caco-2 cells). Hence, this simple and harmless nanotechnological approach could be a key-step in making innovative nanomaterials for nutraceuticals delivering