https://www.selleckchem.com/products/Perifosine.html Polypeptides are useful in designing protein-polypeptide conjugates for therapeutic applications; however, they are not satisfactory in improving the stability of therapeutic proteins and extending their in vivo half-life. Here we show that thermally-induced self-assembly (TISA) of elastin-like polypeptide diblock copolymer fused interferon alpha (IFNα-ELPdiblock) into a spherical micelle can dramatically enhance the proteolytic stability of IFNα. Notably, the circulation half-life of IFNα-ELPdiblock micelle (54.7 h) is 124.3-, 5.7-, and 1.4-time longer than those of free IFNα (0.44 h), freely soluble IFNα-ELP (9.6 h), and PEGylated IFNα (39.0 h), respectively. Importantly, in a mouse model of ovarian tumor, IFNα-ELPdiblock micelle exhibited significantly enhanced tumor retention and antitumor efficacy over free IFNα, freely soluble IFNα-ELP, and even PEGylated IFNα. These findings provide a thermoresponsive supramolecular strategy of TISA to design protein-diblock copolypeptide conjugate micelles with enhanced stability and pharmacology.Excessive activation of NF-κB in macrophages contributes to the onset and exacerbation of inflammatory disorders. The NEMO binding domain (NBD) peptide is an NF-κB inhibitor peptide that binds to NEMO, one of components of the IκB kinase (IKK) complex, and inhibits the IKK kinase activity, in the cytosol. Because of this property, the NBD peptide is expected to inhibit NF-κB activation in macrophages. In this study, we developed a delivery carrier for NBD based on small extracellular vesicles (sEVs), which are membrane vesicles released from cells. We constructed fusion proteins comprising Gag (an sEV tropic protein) and one, three, or six repeats of NBD peptide (Gag-1NBD, Gag-3NBD, and Gag-6NBD, respectively) to load the NBD peptide to the inner space of the sEVs, and attempted the intracellular delivery of the NBD peptide to macrophages using Gag-NBD-loaded sEVs (nNBD-sEVs). The