One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles Duro Castaño, Aroa Rodríguez Arco, Laura A.D.-C. and G.B. acknowledge the Royal Society (Newton International Fellowship scheme 2017.NF171487) and EU H2020 MSCA-IF-792957 SPeNTa-Brain. The authors thank the ERC for the consolidator award (CheSSTaG 769798), EPSRC Established Career Fellowship (EP/N026322/1) and Jeol and DENS Solutions for sponsoring LPR salary, and part of C.D.P. and G.M. studentships. L.R.-A. thanks the UK's ESPRC for funding her salary (Grant EP/N026322/1) and acknowledges support by the Spanish State Research Agency (Spanish Ministry of Science and Innovation) through Juan de la Cierva Incorporacion Fellowship (IJC2018-037951-I). The authors thank Prof. Modesto T. Lopez-Lopez (University of Granada, Spain) for helpful discussions about gel rheology, Dr. Inmaculada Conejos (CIPF, Valencia, Spain) for her help with the CD, and Gabriel Ing (University College London, UK) for his support with transmission electron microscopy. Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization selfassembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering. 2022-03-01T12:09:00Z 2022-03-01T12:09:00Z 2021-11-11 journal article Biomacromolecules 2021, 22, 5052−5064. [https://doi.org/10.1021/acs.biomac.1c01039] http://hdl.handle.net/10481/73046 10.1021/acs.biomac.1c01039 eng info:eu-repo/grantAgreement/EC/H2020/792957 info:eu-repo/grantAgreement/EC/H2020/769798 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ open access Atribución-NoComercial-SinDerivadas 3.0 España American Chemical Society