Fluorescence Switching in pH-Responsive Poly(amidoamine) Hydrogel Networks Containing Gold Nanoparticles and Carbon Nanodots for Potential Real-Time Tumor pH Monitoring

We developed a poly(amidoamine)-based nanocomposite hydrogel incorporating carbon dots (CDs) and gold nanoparticles (AuNPs) to create a 3D fluorescent network responsive to pH variations within the tumor microenvironment (TME; pH 5.5–7.4). The system exploits biocompatible acrylamide end-capped oligomers obtained by polyaddition of l-arginine and methylenebis(acrylamide), which exhibit pH-sensitive conformations that modulate interparticle distances and, consequently, fluorescence intensity. Optimal concentrations of CDs and AuNPs were identified to promote an antenna effect via surface electron interactions, enhancing the fluorescence. The fluorescence quantum yield peaked at pH 6.4 due to network compaction and declined at both lower (5.5) and physiological pH (7.4), with the latter due to stronger CD–AuNP interactions and polymer collapse. This behavior enables the hydrogel to act as a real-time pH sensor suitable for bioimaging applications. The hydrogel produced by this method can be, in principle, readily converted into nanogels with tunable size and morphology, thus offering potential for injectable delivery and broader biomedical use. These findings support the application of l-ARGO7@CDs/AuNPs nanogels for fluorescence-guided tumor detection and pH-responsive monitoring of therapeutic outcomes, opening opportunities for personalized oncological treatments.