Biomedical Engineering Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126808. doi: 10.1016/j.ijbiomac.2023.126808. Epub 2023 Sep 9.
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.
尽管已经做出了许多努力，但乳腺癌仍然是最致命的癌症之一，其治疗面临着与癌症药物副作用和转移相关的挑战。将 3D 打印和纳米载体结合使用为癌症治疗创造了新的机会。在这项工作中，使用了 3D 打印的含有阿霉素负载的尼莫司汀（Nio-DOX@GT-AL）的明胶-海藻酸钠纳米复合材料作为一种先进的潜在 pH 敏感药物传递系统。评估了纳米复合材料和对照物（Nio-DOX 和游离 DOX）的形态、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。结果表明，得到的尼莫司汀具有球形形状，尺寸为 60-80nm。Nio-DOX@GT-AL 和 Nio-DOX 呈现出持续的药物释放和生物降解性。细胞毒性分析表明，所设计的 Nio-DOX@GT-AL 支架对乳腺癌细胞（MCF-7）具有 90%的细胞毒性，而对非肿瘤乳腺细胞系（MCF-10A）的细胞毒性<5%，这明显优于对照样品的抗肿瘤作用。划痕试验作为细胞迁移的指标表明，覆盖表面减少了近 60%。基因表达可以为工程纳米载体的抗肿瘤作用提供解释，其显著降低了促进转移的基因（Bcl2、MMP-2 和 MMP-9）的表达，并显著增强了促进凋亡的基因（CASP-3、CASP-8 和 CASP-9）的表达和活性。此外，观察到对转移相关基因（Bax 和 p53）的显著抑制。此外，流式细胞术数据表明，Nio-DOX@GT-AL 大大降低了坏死并增强了凋亡。这项研究的结果可以证实，采用 3D 打印和尼莫司汀制剂可以成为设计用于有效药物传递应用的新型纳米载体的有效策略。
