par Abrishami, Amir ;Shavandi, Armin
Référence (09-10 December 2025: Kortrijk, Belgium), BSTE 2025 – 12th Belgian Symposium on Tissue Engineering
Publication Publié, 2025-12-10
Abstract de conférence
Résumé : Nanoparticle-based cancer theranostics face challenges because 2D assays lack tumor complexity, and animal models have ethical and translational limitations. Tissue engineering provides new opportunities to develop biomimetic 3D tumor models for mechanistic studies of nanomedicines. We designed a vascularized, volumetrically printed colorectal tumor model with perfusable channels and a tumor cell-laden core. This platform enables controlled administration, spatial monitoring, and quantitative evaluation of therapeutic nanomaterials. Four MnO₂ quantum dot formulations with distinct surface chemistries were synthesized via green routes and characterized for their activity as peroxidase (POD), catalase (CAT), chemodynamic (CD), and photothermal (PT) effects. These include cysteine-coated (Cys–MnO₂), casein-coated (Cas–MnO₂), polydopamine-coated (PDA@Cys–MnO₂), and PEGylated PDA@Cys–MnO₂. The responsiveness of nanoparticles was evaluated kinetically in solution and confirmed by treating colorectal cancer 2D cultures and the 3D tumor model. Cys–MnO₂ exhibited superior catalytic activity, with Km values 2–3 times lower than those of Cas–MnO₂ (POD: 1.24 vs. 6.05 mM; CAT: 7.34 vs. 20.07 mM), indicating higher substrate affinity and catalytic efficiency. In contrast, Cas–MnO₂ offered 35-40% stronger fluorescence intensity. PDA coatings enabled photothermal reactivity, and PEGylation improved colloidal stability and therapeutic synergy. In 2D colorectal cancer cultures, all formulations enhanced ROS generation and cytotoxicity, but the differences between groups were modest. The 3D tumor model, however, revealed spatially distinct responses driven by surface chemistry. Cytotoxicity assays showed that PEG–PDA@Cys-MnO2 penetrated into the core, combining photothermal and chemodynamic effects to achieve over 80% tumor cell death within 48 hours. In conclusion, the volumetrically printed 3D tumor model provided mechanistic insights into nanoparticle–tumor interactions that were inaccessible with conventional 2D assays. Our findings demonstrate how nanoparticle surface chemistry shapes reactivity, efficacy, and penetration in a biomimetic tumor microenvironment. Future studies will integrate immune components and patient-derived cells to advance this platform toward personalized nanotheranostics.