Curcio, ManuelaDíaz Gómez, LuisCirillo, GiuseppeNicoletta, Fiore PasqualeLeggio, AntonellaLemma, Francesca2021-03-122021-03-122021Pharmaceutics 2021, 13(3), 304; https://doi.org/10.3390/pharmaceutics13030304http://hdl.handle.net/10347/24738Drug targeting of tumor cells is one of the great challenges in cancer therapy; nanoparticles based on natural polymers represent valuable tools to achieve this aim. The ability to respond to environmental signals from the pathological site (e.g., altered redox potential), together with the specific interaction with membrane receptors overexpressed on cancer cells membrane (e.g., CD44 receptors), represent the main features of actively targeted nanoparticles. In this work, redox-responsive micelle-like nanoparticles were prepared by self-assembling of a hyaluronic acid–human serum albumin conjugate containing cystamine moieties acting as a functional spacer. The conjugation procedure consisted of a reductive amination step of hyaluronic acid followed by condensation with albumin. After self-assembling, nanoparticles with a mean size of 70 nm and able to be destabilized in reducing media were obtained. Doxorubicin-loaded nanoparticles modulated drug release rate in response to different redox conditions. Finally, the viability and uptake experiments on healthy (BALB-3T3) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a drug vector in cancer therapyeng© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Hyaluronic acidHuman serum albuminPolysaccharide-protein conjugateMicelle-like nanoparticlesRedox-responsiveActive targetingCancer therapyjournal article10.3390/pharmaceutics130303041999-4923open access