3D bioprinted melanoma constructs reveal delivery-dependent efficacy of phytochemical-gold nanoparticle formulations
Biomedical Materials (Bristol), cilt.21, sa.3, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 21 Sayı: 3
- Basım Tarihi: 2026
- Doi Numarası: 10.1088/1748-605x/ae5ee7
- Dergi Adı: Biomedical Materials (Bristol)
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, EMBASE, INSPEC, MEDLINE
- Anahtar Kelimeler: gold nanocarriers, melanoma A375, phytochemicals, curcumin, thymoquinone, EGCG, 3D scaffold
- Boğaziçi Üniversitesi Adresli: Evet
Özet
This study investigates the efficacy of phytochemical nanoformulations—specifically curcumin and thymoquinone (TQ) delivered via gold nanoparticles (AuNPs)—against melanoma A375 cells in both 2D and 3D bioprinted gelatin-alginate scaffolds. Phytochemicals such as curcumin, TQ, epigallocatechin gallate, and betulin exhibit multi-target anticancer effects, but their clinical translation is limited by poor solubility, rapid metabolism, and low tumor penetration. We compared free phytochemicals, AuNP co-administration, and AuNP-phytochemical conjugates, assessing their effects on viability, ROS generation, and mitochondrial membrane potential over time. In 2D cultures, all agents exhibited dose-dependent cytotoxicity, with curcumin and TQ proving to be the most potent. However, in 3D scaffolds mimicking tumor microenvironments, only AuNP-phytochemical conjugates sustained mitochondrial and redox stress, overcoming adaptation barriers and providing durable suppression of melanoma viability. Free and co-administered agents displayed metabolic rebound and limited efficacy due to diffusion constraints and extracellular matrix-driven resistance. Unlike prior studies that investigate either free phytochemicals or nanoparticle delivery in isolation, this work integrates 2D and 3D bioprinted A375 melanoma constructs to directly compare free, co-administered, and gold-nanoparticle–conjugated phytochemicals. We show that only conjugated AuNP–phytochemical formulations sustain mitochondrial and redox stress long enough to overcome 3D adaptation barriers, establishing a delivery-strategy–dependent framework for preclinical evaluation of phytochemical nanomedicines.