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3D bioprinted melanoma constructs reveal delivery-dependent efficacy of phytochemical-gold nanoparticle formulations
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DOI：10.1088/1748-605X/ae5ee7.png)
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Abstract
En 中文
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.
Keywords:
phytochemical nanoformulations
gold nanoparticles
melanoma A375 cells
3D bioprinted scaffolds
mitochondrial stress
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