尽管付出了许多努力，乳腺癌仍然是最致命的癌症之一，并且其治疗面临与癌症药物副作用和转移有关的挑战。将3D打印和纳米载体相结合在癌症治疗方面创造了新的机会。在这项工作中，我们招募了含有阿霉素-载荷结晶体乳化悬浮液（Nio-DOX@GT-AL）的3D打印明胶-藻酸盐纳米复合材料作为一种新型潜在的pH敏感型药物缓释系统。我们对纳米复合材料和对照组（Nio-DOX和自由-DOX）的形态学、降解、药物释放、流式细胞术、细胞细胞毒性、细胞迁移、半胱天冬酶活性和基因表达进行了评估。结果表明，所得的结晶体乳化悬浮液具有球形形状和60-80纳米的尺寸。Nio-DOX@GT-AL和Nio-DOX表现出持续的药物释放和生物降解性。细胞毒性分析显示，工程化的Nio-DOX@GT-AL支架对乳腺癌细胞（MCF-7）具有90%的细胞毒性，而对非肿瘤性乳腺细胞系（MCF-10A）的细胞毒性低于5%，显著高于对照样品的抗肿瘤效果。划痕试验作为细胞迁移的指标表明，覆盖表面减少了近60%。基因表达可以解释工程纳米载体的抗肿瘤效应，其显著降低了转移促进基因（Bcl2、MMP-2和MMP-9）的表达，并显著增加了促进凋亡的基因（CASP-3、CASP-8和CASP-9）的表达和活性。此外，还观察到对转移相关基因（Bax和p53）有显著的抑制作用。此外，流式细胞术数据显示，Nio-DOX@GT-AL显著减少了坏死，并显著增加了凋亡。本研究的发现表明，应用3D打印和结晶体乳化悬浮液制剂可以是设计高效药物传递应用的新型纳米载体的有效策略。版权所有©2023 Elsevier B.V.发布。

Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining 3D printing and nanocarriers has created new opportunities in cancer treatment. In this work, 3D-printed gelatin-alginate nanocomposites containing doxorubicin-loaded niosomes (Nio-DOX@GT-AL) were recruited as an advanced potential pH-sensitive drug delivery system. Morphology, degradation, drug release, flow cytometry, cell cytotoxicity, cell migration, caspase activity, and gene expression of nanocomposites and controls (Nio-DOX and Free-DOX) were evaluated. Results show that the obtained niosome has a spherical shape and size of 60-80 nm. Sustained drug release and biodegradability were presented by Nio-DOX@GT-AL and Nio-DOX. Cytotoxicity analysis revealed that the engineered Nio-DOX@GT-AL scaffold had 90 % cytotoxicity against breast cancer cells (MCF-7), whereas exhibited <5 % cytotoxicity against the non-tumor breast cell line (MCF-10A), which was significantly more than the antitumor effect of the control samples. Scratch-assay as an indicator cell migration demonstrated a reduction of almost 60 % of the covered surface. Gene expression could provide an explanation for the antitumor effect of engineered nanocarriers, which significantly reduced metastasis-promoting genes (Bcl2, MMP-2, and MMP-9), and significantly enhanced the expression and activity of genes that promote apoptosis (CASP-3, CASP-8, and CASP-9). Also, considerable inhibition of metastasis-associated genes (Bax and p53) was observed. Moreover, flow-cytometry data demonstrated that Nio-DOX@GT-AL decreased necrosis and enhanced apoptosis drastically. The findings of this research can confirm that employing 3D-printing and niosomal formulation can be an effective strategy in designing novel nanocarriers for efficient drug delivery applications.Copyright © 2023. Published by Elsevier B.V.