GSH-Responsive Shape-Transformable Nanotheranostics for Dual-Modal T₁/T₂ MRI-Guided Enhanced PDT of Nasopharyngeal Carcinoma

Based on the properties of photodynamic therapy (PDT) and magnetic resonance imaging (MRI), combining them to construct multifunctional nanotheranostics can leverage strengths and avoid weaknesses for tumor diagnosis and treatment. However, certain problems remain unsolved, notably the short observation window caused by insufficient retention time. In this study, a GSH-responsive shape-transformable nanotheranostics Gd-Ce6-FFVLGGGC-SS-PEG are designed (abbreviated as GdCFS) by combining a single metal Gd with Ce6, and peptide (Phe-Phe-Val-Leu-Gly-Gly-Gly-Cys) disulfide-conjugated with polyethylene glycol (PEG) to perform dual-modal T-1/T-2 MRI specifically at the tumor site. Due to its amphiphilic features, GdCFS can self-assemble to spherical nanoparticles, while transforming to nanofibers (NFs) in the presence of intracellular overexpressed GSH stimuli. After NFs formation, the hydrophobic core of GdCFS is exposed, resulting in T-1 positive contrast enhancement, whereas NFs can simultaneously achieve T-2 negative contrast enhancement. Furthermore, GSH depletion can cause imbalance in intracellular redox state, ultimately improving PDT efficacy. GdCFS benefits from the shape-transformation in terms of sufficient retention time, thus positively minimizing the toxicity risk. On the tumor model of nasopharyngeal carcinoma, in vivo and in vitro outcomes confirm that GdCFS can be a promising candidate for early diagnosis, real-time monitoring, and precise treatment of tumors with great biocompatibility.