A cellulose nanocrystal (CNC)-annealed hydrogel (CAH) structure, including doxorubicin (DOX) and 2-deoxy-d-glucose (2DG), was developed for local chemo-metabolic therapy (LCMT) of melanoma. DOX has been used as a chemotherapeutic agent because of its intercalation into DNA and generation of free radicals. 2DG has been used as a glycolytic inhibitor in multiple metabolic therapies in combination with DOX. Covalent and non-covalent (i.e., ionic and hydrogen bonding) binding approaches between CNC and drug cargo (i.e., DOX and 2DG) were used to tune the rheological properties of the CAH structure to achieve sustained drug release. Reduction of reduced nicotinamide adenine dinucleotide phosphate, adenosine triphosphate, and mitochondrial membrane potential, and elevation of cellular reactive oxygen species and cleaved caspases 3 and 7 were observed following treatment with CNC/DOX/2DG in B16F10 cells. Glutathione depletion, enhanced lipid peroxidation, and decreased lactate levels were observed in the CNC/DOX/2DG group. After intratumoral injection of the CNC/DOX/2DG hydrogel into B16F10 tumor-bearing mice, stronger tumor growth suppression and anti-recurrence capabilities were observed. These findings imply that the viscoelastically modulated CAH system can be a strong candidate for LCMT of melanoma.

中文翻译：

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纤维素纳米晶退火水凝胶系统用于黑色素瘤的局部化学代谢治疗


纤维素纳米晶体 （CNC） 退火水凝胶 （CAH） 结构，包括阿霉素 （DOX） 和 2-脱氧-d-葡萄糖 （2DG），被开发用于黑色素瘤的局部化学代谢治疗 （LCMT）。DOX 已被用作化疗剂，因为它嵌入 DNA 并产生自由基。2DG 已与 DOX 联合用于多种代谢疗法中的糖酵解抑制剂。CNC 和药物货物 （即 DOX 和 2DG） 之间的共价和非共价 （即离子键和氢键） 结合方法用于调节 CAH 结构的流变特性，以实现药物的持续释放。在 B16F10 细胞中用 CNC/DOX/2DG 处理后，观察到烟酰胺腺嘌呤二核苷酸磷酸、三磷酸腺苷和线粒体膜电位降低，细胞活性氧和裂解的半胱天冬酶 3 和 7 升高。在 CNC/DOX/2DG 组中观察到谷胱甘肽耗竭、脂质过氧化增强和乳酸水平降低。将 CNC/DOX/2DG 水凝胶瘤内注射到 B16F10 荷瘤小鼠体内后，观察到更强的肿瘤生长抑制和抗复发能力。这些发现意味着粘弹性调制的 CAH 系统可以成为黑色素瘤 LCMT 的有力候选者。