CD44-targeted nanoparticles with GSH-responsive activity as powerful therapeutic agents against breast cancer

DOX-loaded nanoparticles able to actively target CD44-receptors and respond to redox stimuli were proposed as non-conventional chemotherapeutic strategy in breast cancer. A covalent conjugate of human serum albumin and hyaluronic acid was prepared and assembled by a GSH-mediated desolvation in disulfide-crosslinked solid nanoparticles with mean diameter of 120 nm ± 3.4. The effective internalization of nanoparticles in cancer cells via CD44-receptors, together with the more efficient intracellular release, resulted in a significant increase of drug efficacy, with IC₅₀ reduced from 0.9959 and 2.516 μg mL^-1 to 0.4014 and 0.3094 μg mL^-1 for MCF-7 and MDA-MB-231, respectively. Conversely, no enhancement in drug toxicity was recorded in healthy MCF-10A cells. The efficacy of the proposed formulation was further investigated in the different biological steps involved in metastasis process, paving the way for further in vivo experiments.